Chapter 20

oncogene, anti-oncogene and growth factor

The biochemistry and molecular biology department of CMU

Relationship of oncogene, anti-oncogene and growth factor

§1 Oncogene

• Oncogenes are cellular genes that can trigger uncontrolled cell proliferation if their sequence is altered or their expression is incorrectly regulated.

• A gene found in viruses or as part of th

e normal genome that is involved in trig

gering cancerous characteristics.

• Control the cell growth and cell differen

tiation.

• virus oncogene (v-onc) and cellular- o

ncogene (c-onc) or proto-oncogene

Virus- oncogene (v-onc)

• Genes are in viruses that can

cause tumors in vivo and

transform the cell in vitro.

In 1910, Peyton Rous found the first retrovirus in a chickens filtrated sarcoma. Rous got the Nobel Prize in Physiology and Medicine in 1966.

Cellular Oncogene (c-onc)

• Genes are in static or low-level

expression state in normal cells

under the normal situation and play

an important role in maintaining the

normal function of cells.

Category and major product of cellular oncogene

1. src family — tyrosine protein kinase

2. ras familiy — P21（ GTPase activity）3. myc familiy — intranuclear DNA binding

protein

4. sis familiy — P28 (similar platelet derived growth factor)

5. myb familiy — intranuclear transcription factor

Product and Function of Proto-oncogene

• Extracellular growth factors

• Transmembrane growth factor receptors

• Intracellular signal transduction proteins

• Intranuclear transcription factors

Mechanisms of Oncogene Activation

• Obtaining promoter or enhancer

• Group translocation or chromosome rearrangements

• Proto-oncogene amplification

• Gene mutation

§2 Anti-oncogene

Tumor suppressor gene (anti-oncegene)

• A gene whose protein products inhibit cell division, thereby preventing uncontrolled cell growth (cancer).

• Coding the restrained protein relati

ng to cell cycle control.

• When tumor suppressive gene is d

eleted and mutated, there is an indu

ced occurrence of tumors.

• Rb gene and P53 gene.

Rb gene

• Rb refers to retinoblastoma.

• The major function of Rb gene is the regulation of cell cycle procession.

Mechanism of action of Rb gene

P53 gene

• P53 gene encodes the protein which molecular weight is 53.

Biologic function of P53 protein

• Suppressing cell cycle

• Suppressing transformation func

tion of some oncogenes

• Monitoring cell DNA damage

• Inducing the cell apoptosis

§3 Growth Factor

Growth Factor

• A kind of signal molecules similar with hormones that are secreted by cells and promote cell proliferation and differentiation.

familiar human growth factor Factor Principal resource Primary function EGF

Submaxillary gland, kidney, duodenal gland

EPO

kidney

HGF

Placenta IFN- γ Activated TH1 and NK cells

IGFNGF

Placent, primarily liver, plasmNeur, submaxillary gland

PDGF Platelets,endothelial cells,placenta TGFα Tumor cell, transforming cell, placenta TGFβ Activated TH1 cells(T-helper) and

natural killer(NK) cells

VEGF Smooth muscle, tumor

Producing second messenger

Intracellular related protein phosphorylated

Binding membrane receptor

Tyrosine kinase activition

Protein kinase

activated

Intranuclear transcription factor activation

genetic

transcription

Binding intracellular receptor

growth factor-receptorcompounds activation related gene

Mechanism of action of growth factor