Chapter 20 oncogene, anti-oncogene and growth factor The biochemistry and molecular biology...
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Transcript of Chapter 20 oncogene, anti-oncogene and growth factor The biochemistry and molecular biology...
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