Carcinogenesis 1-3 Flashcards
What is the difference between an oncogene and a tumor suppressor gene?
Oncogenes are like the gas pedal of a car. They promote proliferation.
Tumor suppressors are like the break of a car. They block proliferation or metastasis.
Describe Loss of Heterozygosity as it relates to Rb gene
A heterozygous individual (Rb and Rb mutant) loses heterozygosity via MITOTIC recombination (bad). One cell inherits two mutant copies of the Rb gene.
Cells in the eyes begin dividing uncontrollably.
How is Rb inherited? What kind of disorder is it? Dominant or Recessive?
Rb frequently presents in a dominant inheritance (because of loss of hetero) but is actually a recessive disorder.
Can also be caused by sporatic mutations
Bilateral Rb mutations put patients at risk for what additional things?
Other cancers. Especially osteosarcomas.
Describe Rb’s role in cell proliferation:
Rb normally inhibits proliferation. However, during the cell cycle, cyclin dependent kinases (CDKs) hyperphosphorylate Rb and INHIBIT its normal function.
This allows cells to progress through the cell cycle.
FAP (familial adenomatous polyposis coli) is inhereted in the ____________ manner. It is classified as a ______ disorder.
What gene is responsible for this disorder?
Dominant—-Recessive
APC
How does the APC protein normally function?
APC prevents B-catenin from entering the nucleus. Without APC, B-cat enters the nucleus and begins uncontrolled transcription of oncogenes (promote replication)
How is BRCA1 involved in cancer formation?
BRCA1 is responsible for forming a complex that assures successful DNA replication.
When KOed, the check is removed.
How does p53 work?
Its the keeper of the genome. P53 is responsible for DNA mutation repair at the checkpoint in the cell cycle.
Frequently KOed by oncoviruses.
Can be a “dominant negative.” One bad copy can inactivate the good copy.
A ______ mutation in the p53 is the most common mutation for p53 cancer cells.
Missense.
p53 needs 4 copies of p53 proteins to function.
One bad copy leads to a more stable tetramer and defective protein.
Also Dominant Negative mutations
Viral Oncogenes usually come from _____________ that are mutated and then put into the viral_______.
host oncogenes
RNA/DNA
How does Gleevac work?
It mimics ATP shape in the ABL (able?) protein kinase pocket.
It is a double glove. It fits the enzyme and mimics ATP.
Is P53 a oncogene or tumor suppressor?
Tumor suppressor.
What is a characteristic of familial Retinoblastomas?
Bilateral tumors.
What do gag, env, and pol genes encode for oncogenic retroviruses?
gag= internal virion protein
env= virus membrane glycoprotein
pol=viral polymerase
