Chapter 20 oncogene, anti-oncogene and growth factor The

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Chapter 20
oncogene, anti-oncogene
and growth factor
The biochemistry and molecular
biology department of CMU
Relationship of oncogene, antioncogene 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 the
normal genome that is involved in
triggering cancerous characteristics.
• Control the cell growth and cell
differentiation.
• virus oncogene (v-onc) and cellularoncogene (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 Protooncogene
• 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
relating to cell cycle control.
• When tumor suppressive gene is
deleted and mutated, there is an
induced 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
function 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
EGF
EPO
HGF
IFN- γ
IGF
NGF
PDGF
TGFα
TGFβ
VEGF
Principal resource
Primary function
Submaxillary gland, kidney,
duodenal gland
kidney
Placenta
Activated TH1 and NK cells
Placent, primarily liver, plasm
Neur, submaxillary gland
Platelets,endothelial cells,placenta
Tumor cell, transforming cell, placenta
Activated TH1 cells(T-helper) and
natural killer(NK) cells
Smooth muscle, tumor
Mechanism of action of growth factor
Binding membrane receptor
Binding intracellular receptor
Tyrosine kinase activition
Intracellular
related protein
phosphorylated
Intranuclear transcription
factor activation
Producing second
messenger
Protein kinase
activated
genetic
transcription
growth factorreceptorcompou
nds activation
related gene
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