oncogene, anti-oncogene and growth factor

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Chapter 20

• oncogene, anti-oncogene and growth factor

The biochemistry and molecular biology department
of CMU
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Relationship of oncogene, anti-oncogene and
growth factor
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1 Oncogene
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• Oncogenes are cellular genes that can trigger
  uncontrolled cell proliferation if their sequence
  is altered or their expression is incorrectly
  regulated.

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• 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 cellular- oncogene
  (c-onc) or proto-oncogene

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Virus- oncogene (v-onc)

• Genes are in viruses that can cause tumors in
  vivo and transform the cell in vitro.

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

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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

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Product and Function of Proto-oncogene

• Extracellular growth factors
• Transmembrane growth factor receptors
• Intracellular signal transduction proteins
• Intranuclear transcription factors

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Mechanisms of Oncogene Activation

• Obtaining promoter or enhancer
• Group translocation or chromosome rearrangements
• Proto-oncogene amplification
• Gene mutation

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2 Anti-oncogene
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Tumor suppressor gene (anti-oncegene)

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

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• 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.

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Rb gene

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

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Mechanism of action of Rb gene
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P53 gene

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

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Biologic function of P53 protein

• Suppressing cell cycle
• Suppressing transformation function of some
  oncogenes
• Monitoring cell DNA damage
• Inducing the cell apoptosis

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3 Growth Factor
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Growth Factor

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

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familiar human growth factor
Factor
Principal resource
Primary function
EGF
Submaxillary gland, kidney, duodenal gland
EPO
HGF
kidney
Placenta
IFN- ?
Activated TH1 and NK cells
IGF
Placent, primarily liver, plasm
NGF
Neur, submaxillary gland
PDGF
Platelets,endothelial cells,placenta
TGFa
Tumor cell, transforming cell, placenta
TGFß
Activated TH1 cells(T-helper) and natural
killer(NK) cells
VEGF
Smooth muscle, tumor
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Mechanism of action of growth factor
Binding membrane receptor
Binding intracellular receptor
Tyrosine kinase activition
Producing second messenger
growth factor-receptorcompounds activation
related gene
Intracellular related protein phosphorylated
Protein kinase activated
genetic transcription
Intranuclear transcription factor activation