Todays topics

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Todays topics

• Tumor suppressor
• Retinoblastoma
• Cell cycle

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Dominant acting genes and cancer

• Cell fusion assay
• using virus or chemical agent, cause cell
  membranes to fuse and nucleic contents to merge

? If you fuse a cancer cell with a normal cell,
will the resulting cell be cancerous or normal?
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Tumor Suppressor Genes

• Function to inhibit the oncogenic process
• Frequently function in a recessive capacity
  (Knudsons two-hit hypothesis)
• If one copy is gone/mutated, second normal allele
  will function.
• If both copies are gone/mutated, cancer can
  progress.
• Replace a single normal copy and cells return to
  normal (cell fusion assay).

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Retinoblastoma
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Tumor suppressor genes inherited versus
noninherited mutatations.
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Why is Rb a tumor suppressor?

• Inhibits cell cycle progression
• If cells cant progress through the cell cycle,
  they cant divide

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Cell Cycle When cells grow and proliferate, they
go through the cell cycle. This includes a
replication of the DNA, and separation into two
equal daughter cells.
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Progression through the cell cycle is controlled
by protein kinases
The mastermind of cell division!

• Cyclins the regulatory subunits that control
  cell-cycle events
• Cyclin-dependent kinases (CDKs) catalytic
  subunit phosphorylate proteins (add a phosphate
  group this can activate a protein) associated
  with a particular cyclin-CDK complex

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CKI CDK Inhibitor Inactivate Cyclin-Dependent
Kinases
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Function of Rb
One or more members of this pathway is mutated in
greater than 90 of human cancers. While Rb is a
rare disorder, understanding the function of the
gene has given us insight into the disregulation
of most cancers.
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Cell Cycle When cells grow and proliferate, they
go through the cell cycle. This includes a
replication of the DNA, and separation into two
equal daughter cells.
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Summary

• Tumor suppressor
• Normally functions to prevent cell growth
• These are lost in cancer
• Retinoblastoma
• A protein that inhibits the transcription factor
  E2F normally prevents transcription of cell
  cycle genes
• Loss of Rb allows transcription of cell cycle
  genes
• Cell cycle
• A Kinase is a protein that adds phosphates to
  another protein. This enables the p-protein to
  have a new function.
• Cyclin/CDK complexes regulate progression through
  the cell cycle
• CDKIs inhibit CDKs

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