Oncogene - Classification

Classification

There are several systems for classifying oncogenes, 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:

Category Examples Cancers Gene functions
Growth factors, or mitogens c-Sis glioblastomas, fibrosarcomas, osteosarcomas, breast carcinomas, and melanomas 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 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, pancreatice cancer, lung cancer, brain cancers, and blood cancers mediate the responses to, and the activation receptors of cell proliferation, migration, differentiation, and survival
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 Involved in organism development, cell cycle regulation, cell proliferation, differentiation, cells survival, and apoptosis
Regulatory GTPases Ras protein adenocarcinomas of the pancreas and colon, thyroid tumors, and myeloid leukemia involved in signalling a major pathway leading to cell proliferation.
Transcription factors myc gene malignant T-cell lymphomas and acute myleoid leukemias breast cancer, pancreatic cancer, retinoblastoma, and small cell lung cancer -They regulate transcription of genes that induce cell proliferation.

More detailed information for the above Table:

  • Growth factors usually secreted by 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. It may also cause production of growth hormones in other parts of the body.
  • Receptor Tyrosine Kinases add phosphate groups to other proteins to turn them on or off. Receptor kinases add phosphate groups to receptor proteins at the surface of the cell (which receive protein signals from outside the cell and transmit 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 like a binary switch (on/off) in growth signaling pathways. Downstream effectors of Ras include Raf, MEK, MEKK, MAPK, ERK, most of which in turn regulate genes that mediate cell proliferation.

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