Oncogene

Last updated
Illustration of how a normal cell is converted to a cancer cell, when an oncogene becomes activated Oncogenes illustration.jpg
Illustration of how a normal cell is converted to a cancer cell, when an oncogene becomes activated

An oncogene is a gene that has the potential to cause cancer. [1] In tumor cells, these genes are often mutated, or expressed at high levels. [2]

Contents

Most normal cells undergo a preprogrammed rapid cell death (apoptosis) if critical functions are altered and then malfunction. Activated oncogenes can cause those cells designated for apoptosis to survive and proliferate instead. [3] Most oncogenes began as proto-oncogenes: normal genes involved in cell growth and proliferation or inhibition of apoptosis. If, through mutation, normal genes promoting cellular growth are up-regulated (gain-of-function mutation), they predispose the cell to cancer and are termed oncogenes. Usually, multiple oncogenes, along with mutated apoptotic or tumor suppressor genes, act in concert to cause cancer. Since the 1970s, dozens of oncogenes have been identified in human cancer. Many cancer drugs target the proteins encoded by oncogenes. [2] [4] [5] [6] Oncogenes are a physically and functionally diverse set of genes, and as a result, their protein products have pleiotropic effects on a variety of intricate regulatory cascades within the cell.

Genes known as proto-oncogenes are those that normally encourage cell growth and division in order to generate new cells or sustain the viability of pre-existing cells. When overexpressed, proto-oncogenes can be inadvertently activated (turned on), which changes them to oncogenes. [7]

There are numerous ways to activate (turn on) oncogenes in cells:

Gene changes or mutations: A person's genetic "coding" may differ in a way that causes an oncogene to always be activated. These types of gene changes can develop spontaneously throughout the course of a person's life or they might be inherited from a parent when a transcription error occurs during cell division. [8]

Cells can frequently switch genes on or off via epigenetic mechanisms rather than actual genetic alterations. Alternately, different chemical compounds that can be linked to genetic material (DNA or RNA) may have an impact on which genes are active. An oncogene may sporadically become activated due to these epigenetic modifications. Visit Gene Alterations and Cancer to learn more about epigenetic alterations.

Chromosomal rearrangement: Every living creature has chromosomes, which are substantial strands of DNA that contain the genes for a cell. A chromosome's DNA sequence may alter each time a cell divides. This could cause a gene to be located near to a proto-oncogene that acts as an "on" switch, keeping it active even when it shouldn't. The cell can develop irregularly with the aid of this new oncogene. [9]

Gene duplication: If one cell has more copies of a gene than another, that cell may produce too much of a certain protein.

The first human oncogene (HRAS), a crucial finding in the field of cancer research, was discovered more than 40 years ago, and since then, the number of novel pathogenic oncogenes has increased steadily. The discovery of specific small-molecule inhibitors that specifically target the different oncogenic proteins and a comprehensive mechanistic analysis of the ways in which oncogenes dysregulate physiological signaling to cause different cancer types and developmental syndromes are potential future advances in the field of cancer research. Investigating the quickly expanding field of oncogene molecular research, the goal of this special issue was to generate practical translational indicators that could be able to meet clinical needs. [10]

Genes that are considered crucial for cancer can be divided into two categories based on whether the harmful mutations in them result in function loss or gain. Gain-of-function mutations of proto-oncogenes drive cells to proliferate when they shouldn't, while loss-of-function mutations of tumor suppressor genes free cells from inhibitions that typically serve to control their numbers. The ability of the mutant genes, known as oncogenes, to steer a specific line of test cells toward malignant proliferation can occasionally be used to identify these later mutations, which have a dominating effect.

Many of them were initially found to induce cancer in animals when they are introduced through viral vector infection, which carries genetic information from a prior host cell. Another method for identifying oncogenes is to look for genes that are activated by mutations in human cancer cells or by chromosomal translocations that may indicate the presence of a gene that is crucial for cancer. [11]

Oncogene as an prognostic markers in cancer therapy

Cancer patients are generally categorized according to clinical parameters in order to tailor their cancer therapy. For example, the separation of patients with acute leukemia into those with lymphocytic leukemia and those with myelocytic leukemia is important, because the optimal treatment for each form is different. Even in a particular disease, the identification of patients with good and poor prognostic potential is helpful, since more aggressive therapy may be needed to achieve a cure in the poor prognostic group. Oncogenes are prognostic markers in certain human cancers. N-myc amplification is an independent determinant in predicting a poor outcome in childhood neuroblastoma. Those children with amplification of N-myc, regardless of stage, will have shortened survival [1,2]. Thus, therapeutic efforts are concentrated on intensifying treatment in this poor prognostic group. [12]

History

The theory of oncogenes was foreshadowed by the German biologist Theodor Boveri in his 1914 book Zur Frage der Entstehung Maligner Tumoren (Concerning the Origin of Malignant Tumors) in which he predicted the existence of oncogenes (Teilungsfoerdernde Chromosomen) that become amplified (im permanenten Übergewicht) during tumor development. [13]

Later on, the term "oncogene" was rediscovered in 1969 by National Cancer Institute scientists George Todaro and Robert Huebner. [14]

The first confirmed oncogene was discovered in 1970 and was termed SRC (pronounced "sarc" as it is short for sarcoma). SRC was first discovered as an oncogene in a chicken retrovirus. Experiments performed by Dr. G. Steve Martin of the University of California, Berkeley demonstrated that SRC was indeed the gene of the virus that acted as an oncogene upon infection. [15] The first nucleotide sequence of v-Src was sequenced in 1980 by A.P. Czernilofsky et al. [16]

In 1976, Drs. Dominique Stéhelin  [ fr ], J. Michael Bishop and Harold E. Varmus of the University of California, San Francisco demonstrated that oncogenes were activated proto-oncogenes as is found in many organisms, including humans. Bishop and Varmus were awarded the Nobel Prize in Physiology or Medicine in 1989 for their discovery of the cellular origin of retroviral oncogenes. [17]

Dr. Robert Weinberg is credited with discovering the first identified human oncogene in a human bladder cancer cell line. [18] [19] The molecular nature of the mutation leading to oncogenesis was subsequently isolated and characterized by the Spanish biochemist Mariano Barbacid and published in Nature in 1982. [20] Dr. Barbacid spent the following months extending his research, eventually discovering that the oncogene was a mutated allele of HRAS and characterizing its activation mechanism.

The resultant protein encoded by an oncogene is termed oncoprotein. [21] Oncogenes play an important role in the regulation or synthesis of proteins linked to tumorigenic cell growth. Some oncoproteins are accepted and used as tumor markers.

Proto-oncogene

A proto-oncogene is a normal gene that could become an oncogene due to mutations or increased expression. Proto-oncogenes code for proteins that help to regulate the cell growth and differentiation. Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products. Upon acquiring an activating mutation, a proto-oncogene becomes a tumor-inducing agent, an oncogene. [22] Examples of proto-oncogenes include RAS, WNT, MYC, ERK, and TRK. The MYC gene is implicated in Burkitt's lymphoma, which starts when a chromosomal translocation moves an enhancer sequence within the vicinity of the MYC gene. The MYC gene codes for widely used transcription factors. When the enhancer sequence is wrongly placed, these transcription factors are produced at much higher rates. Another example of an oncogene is the Bcr-Abl gene found on the Philadelphia chromosome, a piece of genetic material seen in Chronic Myelogenous Leukemia caused by the translocation of pieces from chromosomes 9 and 22. Bcr-Abl codes for a tyrosine kinase, which is constitutively active, leading to uncontrolled cell proliferation. (More information about the Philadelphia Chromosome below)

Activation

From proto-oncogene to oncogene Ch1-oncogene.svg
From proto-oncogene to oncogene

The proto-oncogene can become an oncogene by a relatively small modification of its original function. There are three basic methods of activation:

  1. A mutation within a proto-oncogene, or within a regulatory region (for example the promoter region), can cause a change in the protein structure, causing
  2. An increase in the amount of a certain protein (protein concentration), caused by
    • an increase of protein expression (through misregulation)
    • an increase of protein (mRNA) stability, prolonging its existence and thus its activity in the cell
    • gene duplication (one type of chromosome abnormality), resulting in an increased amount of protein in the cell
  3. A chromosomal translocation (another type of chromosome abnormality)
    • There are 2 different types of chromosomal translocations that can occur:
    1. translocation events which relocate a proto-oncogene to a new chromosomal site that leads to higher expression
    2. translocation events that lead to a fusion between a proto-oncogene and a 2nd gene (this creates a fusion protein with increased cancerous/oncogenic activity)
      • the expression of a constitutively active hybrid protein. This type of mutation in a dividing stem cell in the bone marrow leads to adult leukemia
      • Philadelphia Chromosome is an example of this type of translocation event. This chromosome was discovered in 1960 by Peter Nowell and David Hungerford, and it is a fusion of parts of DNA from chromosome 22 and chromosome 9. The broken end of chromosome 22 contains the "BCR" gene, which fuses with a fragment of chromosome 9 that contains the "ABL1" gene. When these two chromosome fragments fuse the genes also fuse creating a new gene: "BCR-ABL". This fused gene encodes for a protein that displays high protein tyrosine kinase activity (this activity is due to the "ABL1" half of the protein). The unregulated expression of this protein activates other proteins that are involved in cell cycle and cell division which can cause a cell to grow and divide uncontrollably (the cell becomes cancerous). As a result, the Philadelphia Chromosome is associated with Chronic Myelogenous Leukemia (as mentioned before) as well as other forms of Leukemia. [23]

The expression of oncogenes can be regulated by microRNAs (miRNAs), small RNAs 21-25 nucleotides in length that control gene expression by downregulating them. [24] Mutations in such microRNAs (known as oncomirs) can lead to activation of oncogenes. [25] Antisense messenger RNAs could theoretically be used to block the effects of oncogenes.

Classification

There are several systems for classifying oncogenes, [26] but there is not yet a widely accepted standard. They are sometimes grouped both spatially (moving from outside the cell inwards) and chronologically (parallelling the "normal" process of signal transduction). There are several categories that are commonly used:

CategoryExamplesCancersGene functions
Growth factors, or mitogens c-Sis glioblastomas, fibrosarcomas, osteosarcomas, breast carcinomas, and melanomas [27] induces cell proliferation.
Receptor tyrosine kinases epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), and vascular endothelial growth factor receptor (VEGFR), HER2/neu Breast cancer, gastrointestinal stromal tumours, non-small-cell lung cancer and pancreatic cancer [28] transduce signals for cell growth and differentiation.
Cytoplasmic tyrosine kinases Src-family, Syk-ZAP-70 family, and BTK family of tyrosine kinases, the Abl gene in CML - Philadelphia chromosome colorectal and breast cancers, melanomas, ovarian cancers, gastric cancers, head and neck cancers, pancreatic cancer, lung cancer, brain cancers, and blood cancers [29] mediate the responses to, and the activation receptors of cell proliferation, migration, differentiation, and survival [30]
Cytoplasmic Serine/threonine kinases and their regulatory subunits Raf kinase, and cyclin-dependent kinases (through overexpression).malignant melanoma, papillary thyroid cancer, colorectal cancer, and ovarian cancer [31] involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and apoptosis [32]
Regulatory GTPases Ras protein adenocarcinomas of the pancreas and colon, thyroid tumors, and myeloid leukemia [33] involved in signalling a major pathway leading to cell proliferation. [34]
Transcription factors myc genemalignant T-cell lymphomas and acute myeloid leukemias, breast cancer, pancreatic cancer, retinoblastoma, and small cell lung cancer [35] regulate transcription of genes that induce cell proliferation.
Transcriptional coactivators YAP, WWTR1 genesglioma, melanoma, lung cancer, breast cancers, and more [36] interact with transcription factor partners to regulate transcription of genes that induce cell proliferation.

Additional oncogenetic regulator properties include:

  • Growth factors are usually secreted by either specialized or non-specialized cells to induce cell proliferation in themselves, nearby cells, or distant cells. An oncogene may cause a cell to secrete growth factors even though it does not normally do so. It will thereby induce its own uncontrolled proliferation ( autocrine loop ), and proliferation of neighboring cells, possibly leading to tumor formation. It may also cause production of growth hormones in other parts of the body.
  • Receptor tyrosine kinases add phosphate groups to other proteins in order to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receives protein signals from outside the cell and transmits them to the inside of the cell). Tyrosine kinases add phosphate groups to the amino acid tyrosine in the target protein. They can cause cancer by turning the receptor permanently on (constitutively), even without signals from outside the cell.
  • Ras is a small GTPase that hydrolyses GTP into GDP and phosphate. Ras is activated by growth factor signaling (i.e., EGF, TGFbeta) and acting as a binary switch (on/off) in growth signaling pathways. Downstream effectors of Ras include three mitogen-activated protein kinases Raf a MAP Kinase Kinase Kinase (MAPKKK), MEK a MAP Kinase Kinase (MAPKK), and ERK a MAP Kinase(MAPK), which in turn regulate genes that mediate cell proliferation. [37]

See also

Related Research Articles

<span class="mw-page-title-main">Tyrosine kinase</span> Class hi residues

A tyrosine kinase is an enzyme that can transfer a phosphate group from ATP to the tyrosine residues of specific proteins inside a cell. It functions as an "on" or "off" switch in many cellular functions.

<span class="mw-page-title-main">Burkitt lymphoma</span> Cancer of the lymphatic system

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).

<span class="mw-page-title-main">Philadelphia chromosome</span> Genetic abnormality in leukemia cancer cells

The Philadelphia chromosome or Philadelphia translocation (Ph) is a specific genetic abnormality in chromosome 22 of leukemia cancer cells. This chromosome is defective and unusually short because of reciprocal translocation, t(9;22)(q34;q11), of genetic material between chromosome 9 and chromosome 22, and contains a fusion gene called BCR-ABL1. This gene is the ABL1 gene of chromosome 9 juxtaposed onto the breakpoint cluster region BCR gene of chromosome 22, coding for a hybrid protein: a tyrosine kinase signaling protein that is "always on", causing the cell to divide uncontrollably by interrupting the stability of the genome and impairing various signaling pathways governing the cell cycle.

<span class="mw-page-title-main">ABL (gene)</span> Human protein-coding gene on chromosome 9

Tyrosine-protein kinase ABL1 also known as ABL1 is a protein that, in humans, is encoded by the ABL1 gene located on chromosome 9. c-Abl is sometimes used to refer to the version of the gene found within the mammalian genome, while v-Abl refers to the viral gene, which was initially isolated from the Abelson murine leukemia virus.

Myc is a family of regulator genes and proto-oncogenes that code for transcription factors. The Myc family consists of three related human genes: c-myc (MYC), l-myc (MYCL), and n-myc (MYCN). c-myc was the first gene to be discovered in this family, due to homology with the viral gene v-myc.

<span class="mw-page-title-main">N-Myc</span> Protein-coding gene in the species Homo sapiens

N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the MYCN gene.

<span class="mw-page-title-main">KIT (gene)</span> Mammalian protein and protein-coding gene

Proto-oncogene c-KIT is the gene encoding the receptor tyrosine kinase protein known as tyrosine-protein kinase KIT, CD117 or mast/stem cell growth factor receptor (SCFR). Multiple transcript variants encoding different isoforms have been found for this gene. KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.

v-Src is a gene found in Rous sarcoma virus (RSV) that encodes a tyrosine kinase that causes a type of cancer in chickens.

<span class="mw-page-title-main">STAT5</span> Protein family

Signal transducer and activator of transcription 5 (STAT5) refers to two highly related proteins, STAT5A and STAT5B, which are part of the seven-membered STAT family of proteins. Though STAT5A and STAT5B are encoded by separate genes, the proteins are 90% identical at the amino acid level. STAT5 proteins are involved in cytosolic signalling and in mediating the expression of specific genes. Aberrant STAT5 activity has been shown to be closely connected to a wide range of human cancers, and silencing this aberrant activity is an area of active research in medicinal chemistry.

<span class="mw-page-title-main">Acute myeloblastic leukemia with maturation</span> Medical condition

Acute myeloblastic leukemia with maturation (M2) is a subtype of acute myeloid leukemia (AML).

<span class="mw-page-title-main">Fibroblast growth factor receptor 1</span> Protein-coding gene in the species Homo sapiens

Fibroblast growth factor receptor 1 (FGFR1), also known as basic fibroblast growth factor receptor 1, fms-related tyrosine kinase-2 / Pfeiffer syndrome, and CD331, is a receptor tyrosine kinase whose ligands are specific members of the fibroblast growth factor family. FGFR1 has been shown to be associated with Pfeiffer syndrome, and clonal eosinophilias.

<span class="mw-page-title-main">ETV6</span> Protein-coding gene in the species Homo sapiens

ETV6 protein is a transcription factor that in humans is encoded by the ETV6 gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly those of hematological tissues. However, its gene, ETV6 frequently suffers various mutations that lead to an array of potentially lethal cancers, i.e., ETV6 is a clinically significant proto-oncogene in that it can fuse with other genes to drive the development and/or progression of certain cancers. However, ETV6 is also an anti-oncogene or tumor suppressor gene in that mutations in it that encode for a truncated and therefore inactive protein are also associated with certain types of cancers.

<span class="mw-page-title-main">PDGFRB</span> Protein-coding gene in the species Homo sapiens

Platelet-derived growth factor receptor beta is a protein that in humans is encoded by the PDGFRB gene. Mutations in PDGFRB are mainly associated with the clonal eosinophilia class of malignancies.

<span class="mw-page-title-main">Proto-oncogene tyrosine-protein kinase Src</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Src, also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. It belongs to a family of Src family kinases and is similar to the v-Src gene of Rous sarcoma virus. It includes an SH2 domain, an SH3 domain and a tyrosine kinase domain. Two transcript variants encoding the same protein have been found for this gene.

<span class="mw-page-title-main">Colony stimulating factor 1 receptor</span> Protein found in humans

Colony stimulating factor 1 receptor (CSF1R), also known as macrophage colony-stimulating factor receptor (M-CSFR), and CD115, is a cell-surface protein encoded by the human CSF1R gene. CSF1R is a receptor that can be activated by two ligands: colony stimulating factor 1 (CSF-1) and interleukin-34 (IL-34). CSF1R is highly expressed in myeloid cells, and CSF1R signaling is necessary for the survival, proliferation, and differentiation of many myeloid cell types in vivo and in vitro. CSF1R signaling is involved in many diseases and is targeted in therapies for cancer, neurodegeneration, and inflammatory bone diseases.

<span class="mw-page-title-main">YES1</span> Protein-coding gene in the species Homo sapiens

Proto-oncogene tyrosine-protein kinase Yes is a non-receptor tyrosine kinase that in humans is encoded by the YES1 gene.

<span class="mw-page-title-main">ABL2</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene.

<i>ERG</i> (gene) Protein-coding gene in the species Homo sapiens

ERG is an oncogene. ERG is a member of the ETS family of transcription factors. The ERG gene encodes for a protein, also called ERG, that functions as a transcriptional regulator. Genes in the ETS family regulate embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis.

<span class="mw-page-title-main">Platelet-derived growth factor receptor A</span>

Platelet-derived growth factor receptor A, also termed CD140a, is a receptor located on the surface of a wide range of cell types. The protein is encoded in the human by the PDGFRA gene. This receptor binds to certain isoforms of platelet-derived growth factors (PDGFs) and thereby becomes active in stimulating cell signaling pathways that elicit responses such as cellular growth and differentiation. The receptor is critical for the embryonic development of certain tissues and organs, and for their maintenance, particularly hematologic tissues, throughout life. Mutations in PDGFRA, are associated with an array of clinically significant neoplasms, notably ones of the clonal hypereosinophilia class of malignancies, as well as gastrointestinal stromal tumors (GISTs).

Clonal hypereosinophilia, also termed primary hypereosinophilia or clonal eosinophilia, is a grouping of hematological disorders all of which are characterized by the development and growth of a pre-malignant or malignant population of eosinophils, a type of white blood cell that occupies the bone marrow, blood, and other tissues. This population consists of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a sufficiently mutated ancestor cell.

References

  1. ↑ Wilbur B, ed. (2009). The World of the Cell (7th ed.). San Francisco, California.{{cite book}}: CS1 maint: location missing publisher (link)
  2. 1 2 Kimball's Biology Pages. Archived 2017-12-31 at the Wayback Machine "Oncogenes" Free full text
  3. ↑ The Nobel Prize in Physiology or Medicine 2002. Illustrated presentation.
  4. ↑ Croce CM (January 2008). "Oncogenes and cancer". The New England Journal of Medicine. 358 (5): 502–511. doi:10.1056/NEJMra072367. PMID   18234754.
  5. ↑ Yokota J (March 2000). "Tumor progression and metastasis". Carcinogenesis. 21 (3): 497–503. doi: 10.1093/carcin/21.3.497 . PMID   10688870.
  6. ↑ The Nobel Prize in Physiology or Medicine 1989 to J. Michael Bishop and Harold E. Varmus for their discovery of "the cellular origin of retroviral oncogenes".
  7. ↑ Niederhuber, John E.; Armitage, James O.; Doroshow, James H.; Kastan, Michael B.; Tepper, Joel E. (2020), "Dedication", Abeloff's Clinical Oncology, Elsevier, pp. v, doi:10.1016/b978-0-323-47674-4.00126-2, ISBN   9780323476744 , retrieved 2023-12-10
  8. ↑ Adler Jaffe, Shoshana; Jacobson, Kendal; Farnbach Pearson, Amy W.; Baca, Lila A.; Dimauro, Nina; Kano, Miria (2023-05-05). ""Did I get into the twilight zone somehow?": sexual and gender minority cancer caregiver experiences during COVID". Cancer Causes & Control. 34 (7): 563–568. doi:10.1007/s10552-023-01708-9. ISSN   0957-5243. PMC   10161178 . PMID   37145262.
  9. ↑ Teh, Bin Tean; Fearon, Eric R. (2020), "Genetic and Epigenetic Alterations in Cancer", Abeloff's Clinical Oncology, Elsevier, pp. 209–224.e2, doi:10.1016/b978-0-323-47674-4.00014-1, ISBN   9780323476744 , retrieved 2023-12-10
  10. ↑ Chen, Qiongfeng; Jin, Jingguang; Guo, Wenhui; Tang, Zhimin; Luo, Yunfei; Ying, Ying; Lin, Hui; Luo, Zhijun (2022-08-08). "PEBP4 Directs the Malignant Behavior of Hepatocellular Carcinoma Cells via Regulating mTORC1 and mTORC2". International Journal of Molecular Sciences. 23 (15): 8798. doi: 10.3390/ijms23158798 . ISSN   1422-0067. PMC   9369291 . PMID   35955931.
  11. ↑ Abuasaker, Baraa; Garrido, Eduardo; Vilaplana, Marta; Gómez-Zepeda, Jesús Daniel; Brun, Sonia; Garcia-Cajide, Marta; Mauvezin, Caroline; Jaumot, Montserrat; Pujol, Maria Dolors; Rubio-Martínez, Jaime; Agell, Neus (2023-01-01). "α4-α5 Helices on Surface of KRAS Can Accommodate Small Compounds That Increase KRAS Signaling While Inducing CRC Cell Death". International Journal of Molecular Sciences. 24 (1): 748. doi: 10.3390/ijms24010748 . ISSN   1422-0067. PMC   9821572 . PMID   36614192.
  12. ↑ Larrick, James W.; Liu, Edison (1989), Benz, Christopher; Liu, Edison (eds.), "Therapeutic applications of oncogenes", Oncogenes, vol. 47, Boston, MA: Springer US, pp. 319–330, doi:10.1007/978-1-4613-1599-5_14, ISBN   978-1-4612-8885-5, PMID   2577004 , retrieved 2023-12-10
  13. ↑ Boveri T (1914). Zur Frage der Entstehung maligner Tumoren. Jena: Gustav Fischer.
  14. ↑ The Emperor of All Maladies, Siddhartha Mukherjee, 2011, p. 363
  15. ↑ Martin GS (June 2001). "The hunting of the Src". Nature Reviews. Molecular Cell Biology. 2 (6): 467–475. doi:10.1038/35073094. PMID   11389470. S2CID   205016442.
  16. ↑ Czernilofsky AP, Levinson AD, Varmus HE, Bishop JM, Tischer E, Goodman HM (September 1980). "Nucleotide sequence of an avian sarcoma virus oncogene (src) and proposed amino acid sequence for gene product". Nature. 287 (5779): 198–203. Bibcode:1980Natur.287..198C. doi:10.1038/287198a0. PMID   6253794. S2CID   4231060.
  17. ↑ Nobel Prize in Physiology or Medicine for 1989 jointly to J. Michael Bishop and Harold E. Varmus for their discovery of "the cellular origin of retroviral oncogenes". Press Release.
  18. ↑ Shih C, Weinberg RA (May 1982). "Isolation of a transforming sequence from a human bladder carcinoma cell line". Cell. 29 (1): 161–169. doi:10.1016/0092-8674(82)90100-3. PMID   6286138. S2CID   12046552.
  19. ↑ Lowry F (5 May 2011). "Robert Weinberg Rewarded for Oncogene Discovery". Medscape. Retrieved 6 February 2020.
  20. ↑ Reddy EP, Reynolds RK, Santos E, Barbacid M (November 1982). "A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene". Nature. 300 (5888): 149–152. Bibcode:1982Natur.300..149R. doi:10.1038/300149a0. PMID   7133135. S2CID   34599264.
  21. ↑ Mitchell RS, Kumar V, Abbas AK, Fausto N (2007). "Chapter 20 - Neoplasms of the Thyroid". Robbins Basic Pathology (8th ed.). Philadelphia: Saunders. ISBN   978-1-4160-2973-1.
  22. ↑ Todd R, Wong DT (1999). "Oncogenes". Anticancer Research. 19 (6A): 4729–4746. PMID   10697588.
  23. ↑ Chial H (2008). "Proto-oncogenes to Oncogenes to Cancer". Nature Education. 1 (1).
  24. ↑ Negrini M, Ferracin M, Sabbioni S, Croce CM (June 2007). "MicroRNAs in human cancer: from research to therapy". Journal of Cell Science. 120 (Pt 11): 1833–1840. doi: 10.1242/jcs.03450 . PMID   17515481.
  25. ↑ Esquela-Kerscher A, Slack FJ (April 2006). "Oncomirs - microRNAs with a role in cancer". Nature Reviews. Cancer. 6 (4): 259–269. doi:10.1038/nrc1840. PMID   16557279. S2CID   10620165.
  26. ↑ "THE Medical Biochemistry Page". Archived from the original on 2021-01-26. Retrieved 2007-03-12.
  27. ↑ Press RD, Misra A, Gillaspy G, Samols D, Goldthwait DA (June 1989). "Control of the expression of c-sis mRNA in human glioblastoma cells by phorbol ester and transforming growth factor beta 1". Cancer Research. 49 (11): 2914–2920. PMID   2655888.
  28. ↑ Gschwind A, Fischer OM, Ullrich A (May 2004). "The discovery of receptor tyrosine kinases: targets for cancer therapy". Nature Reviews. Cancer. 4 (5): 361–370. doi:10.1038/nrc1360. PMID   15122207. S2CID   6939454.
  29. ↑ Summy JM, Gallick GE (December 2003). "Src family kinases in tumor progression and metastasis". Cancer and Metastasis Reviews. 22 (4): 337–358. doi:10.1023/A:1023772912750. PMID   12884910. S2CID   12380282.
  30. ↑ Thomas SM, Brugge JS (1 November 1997). "Cellular functions regulated by Src family kinases". Annual Review of Cell and Developmental Biology. 13 (1): 513–609. doi:10.1146/annurev.cellbio.13.1.513. PMID   9442882.
  31. ↑ Garnett MJ, Marais R (October 2004). "Guilty as charged: B-RAF is a human oncogene". Cancer Cell. 6 (4): 313–319. doi: 10.1016/j.ccr.2004.09.022 . PMID   15488754.
  32. ↑ Leicht DT, Balan V, Kaplun A, Singh-Gupta V, Kaplun L, Dobson M, Tzivion G (August 2007). "Raf kinases: function, regulation and role in human cancer". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1773 (8): 1196–1212. doi:10.1016/j.bbamcr.2007.05.001. PMC   1986673 . PMID   17555829.
  33. ↑ Bos JL (September 1989). "ras oncogenes in human cancer: a review". Cancer Research. 49 (17): 4682–4689. PMID   2547513.
  34. ↑ Hilgenfeld R (December 1995). "Regulatory GTPases". Current Opinion in Structural Biology. 5 (6): 810–817. doi:10.1016/0959-440X(95)80015-8. PMID   8749370.
  35. ↑ Felsher DW, Bishop JM (August 1999). "Reversible tumorigenesis by MYC in hematopoietic lineages". Molecular Cell. 4 (2): 199–207. doi: 10.1016/S1097-2765(00)80367-6 . PMID   10488335.
  36. ↑ Zanconato, Francesca; Cordenonsi, Michelangelo; Piccolo, Stefano (2016-06-13). "YAP/TAZ at the Roots of Cancer". Cancer Cell. 29 (6): 783–803. doi:10.1016/j.ccell.2016.05.005. ISSN   1535-6108. PMC   6186419 . PMID   27300434.
  37. ↑ Cargnello M, Roux PP (March 2011). "Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases". Microbiology and Molecular Biology Reviews. 75 (1): 50–83. doi:10.1128/MMBR.00031-10. PMC   3063353 . PMID   21372320.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.