oncogenes and tumor suppressor genes

genetically recessive

Defective Tumor suppressor genes; ex. p53, Rb

retroviral oncogenes ex

Each encodes a protein that acts at different steps in the pathway of normal cellular growth regulation; ex. Growth factor, Growth factor receptor, Protein kinase, Monomeric G protein, Transcription factor

Genetically dominant

Oncogenes; analogous to a car with a "stuck accelerator". examples: v-sis, v-erb-B, v-src, v-ras, v-myc

v-myc

Overexpression of "normal" form is sufficient to cause cancer

Tumor virus types

RNA & DNA tumor viruses

Retrovirus

RNA tumor virus; Rous sarcoma virus (RSV), Avian lymphoid leukosis virus (ALV), contain oncogenes

v-ras & c-ras

These oncogenes cause cancer by short-circuiting the usual controls leading to unregulated signaling and cell division

v-er-b

This receptor appears to stimulate the cells constitutively (permanently), with or without EGF, thereby leading to uncontrolled cell division

v-ras

binds GTP but fails to hydrolyze the GTP and this results in uncontrolled cell division. Mutant form is commonly found in bladder cancer

Oncogenes

cancer-causing genes that trigger cancer growth; transforms the infected cells so they divide out of control and form tumors

Transcription factor

ex v-myc, v-fos, v-jun; Myc is normally expressed in response to growth factor stimulation of cells and induces the transcription of other genes involved in triggering cells to enter S phase

Protein Kinase

ex v-src (for sarcoma). The src oncogene encodes a protein tyrosine kinase v-src

Growth factor receptor

ex. v-erb-B oncogene from avian (bird) erythroblastosis virus; The oncogene encodes a protein tyrosine kinase that resembles a truncated form of the epidermal derived growth factor (EGF) receptor but lacks the growth factor binding domain and part of the cytoplasmic domain

Monomeric G protein

ex. v-ras. The ras oncogene encodes a small G protein. In normal cells growth factor receptors activate SOS, and SOS activates Ras binding to GTP

Growth factor

ex. v-sis oncogene from Simian (monkey) sarcoma virus; This oncogene resembles platelet derived growth factor (PDGF). If the infected cells contains PDGF receptors the v-sis protein will result in an autocrine stimulation and uncontrolled cell division.

v-src

located at the cytoplasmic side of the plasma membrane. Its also permanently active, so that it continuously phosphorylates proteins leading to uncontrolled cell division

proto-oncogenes

normal host genes involved in regulating the cell cycle and cell division; become true oncogenes when they are overexpressed, mutated, or expressed at the wrong time

gag, pol (polymerase) and env (envelope) genes

these genes are contained in retroviruses and are essential for the normal replication and life cycle of the virus