The Genetic Basis of Cancer
I. Cancer and the cell cycle
A. Cancer cells overgrow each other
1. They do not have contact inhibition
B. Cancer cells bypass cell cycle “checkpoints” designed to regulate the
proliferation of the cell
C. Checkpoints are the cell cycle gatekeepers: only “normal” cells are able to enter
1. G1 to S checkpoint
II. Cancer and apoptosis
A. Cell death is a part of normal cellular biology
B. Caspases play a role in inactivating cellular proteins
C. Cancers not only proliferate too much, they also die too little
III. Is cancer a genetic disease?
A. The cancerous state is clonally inherited
B. Viruses can induce the formation of cancer
1. Like a wart
2. HPV
C. Cancer can be induced by DNA mutagens (carcinogen)
D. Certain types of cancer can run in families
E. Certain white blood cell cancers are associated with chromosomal translocations
F. Mutations in oncogenes and tumor suppressors
1. Mutant oncogenes actively promote cancer
2. Mutant tumor suppressors fail to repress progression
3. Too much gas pedal and not enough brake
G. Viral oncogenes
1. Virus picks up mRNA and turns it into a human gene
2. Gives it back to human, but it’s broken
3. Oncogenetic gene causes damage and cancer
IV. Oncogenes: c-H-ras
A. Mutant cellular oncogenes
1. Mutations of two major types
a) Promoter changes
(1) Gene looks fine, but the promoter is busted
b) Gene mutations/deletions
B. Normal Ras protein signaling
1. Extracellular signal influences the state of the Ras protein
2. Bound by GTP to become active
a) GDP bound is inactive
b) Intrinsic GTPase to shut itself off after a short time
c) Default brake
3. Active Ras protein transduces signal to the nucleus
4. This signal regulates the transcription of genes involved in cell division
5. Cell division occurs in a controlled fashion
I. Cancer and the cell cycle
A. Cancer cells overgrow each other
1. They do not have contact inhibition
B. Cancer cells bypass cell cycle “checkpoints” designed to regulate the
proliferation of the cell
C. Checkpoints are the cell cycle gatekeepers: only “normal” cells are able to enter
1. G1 to S checkpoint
II. Cancer and apoptosis
A. Cell death is a part of normal cellular biology
B. Caspases play a role in inactivating cellular proteins
C. Cancers not only proliferate too much, they also die too little
III. Is cancer a genetic disease?
A. The cancerous state is clonally inherited
B. Viruses can induce the formation of cancer
1. Like a wart
2. HPV
C. Cancer can be induced by DNA mutagens (carcinogen)
D. Certain types of cancer can run in families
E. Certain white blood cell cancers are associated with chromosomal translocations
F. Mutations in oncogenes and tumor suppressors
1. Mutant oncogenes actively promote cancer
2. Mutant tumor suppressors fail to repress progression
3. Too much gas pedal and not enough brake
G. Viral oncogenes
1. Virus picks up mRNA and turns it into a human gene
2. Gives it back to human, but it’s broken
3. Oncogenetic gene causes damage and cancer
IV. Oncogenes: c-H-ras
A. Mutant cellular oncogenes
1. Mutations of two major types
a) Promoter changes
(1) Gene looks fine, but the promoter is busted
b) Gene mutations/deletions
B. Normal Ras protein signaling
1. Extracellular signal influences the state of the Ras protein
2. Bound by GTP to become active
a) GDP bound is inactive
b) Intrinsic GTPase to shut itself off after a short time
c) Default brake
3. Active Ras protein transduces signal to the nucleus
4. This signal regulates the transcription of genes involved in cell division
5. Cell division occurs in a controlled fashion
