Flashcards in Neoplasia II/III Deck (25):
Markers of clonality include...
methylation patterns of specific genes or indicators of identical gene rearrangements (Ig or T cell isotypes)
Four classes of genes that are targets for alterations that cause autonomous proliferation of cells
Growth promoting proto-oncogenes
growth-inhibiting tumor suppressor genes
Genes that regulate apoptosis
Genes involved in DNA repair
What is transformation?
Attainment of the capacity for autonomous growth
in vitro - can grow without GFs and make colonies that override contact inhibition
What is tumor progression?
Growth of a transformed cell from a single cell to a clone of cells to a population with the ability to invade and metastisize
Seven fundamental changes in cell physiology that determine malignant phenotype?
1. Self sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Defects in DNA repair
5. Limitless replicative potential
6. Sustained angiogenesis
7. Ability to invade and metastasize
Progression through the cell cycle is regulated by...
Cyclins and cyclin dependent kinases
What does Cyclin D do?
Activates CDK, which P-ates RB, which is an ON-OFF for the cell cycle
What does RB do?
Acts as break to inhibit cells from going from G0/G1 into S phase. P-ation of RB causes dissociation of RB from E2F and permits replication.
_____ regulates mitotic prophase
_____ regulates nuclear division
How does p53 work?
Activates p21 to inhibit replication of damaged cells. If cell can't be repaired, triggers apoptosis.
When can the cell cycle stop damaged cell duplication
G1/S multiplication checkpoint occurs through
Mitogenic stimulation in cancer is often associated with...
Constitutively active ras, HER2/neu
Most important signal transducing protein to remember?
Most common abnormality of dominant oncogenes.
Colon, Pancreas, Thyroid especially
Philadelphia Chromosome (CML) is associated with what mutation?
c-abl. Increases in tyrosine kinase activity
Most important nuclear regulatory protein to remember? What does it do?
Immediate early growth response genes.
Assoc. with Burkitt's and neuroblastoma
p53 is especially associated with which cancers?
Colon, breast, lung
How does Neurofibromatosis happen
NF-1 enhanced Ras-GTPase to downregulate Ras
overexpression of _____ is a common way that cancers may try to turn off apoptosis
Four important tumor repair gene mutations..
Herditary non-polyposis cancer syndrome
ataxia-telangiectasia/Bloom Syndrome/Fanconi anemia
BRCA1 and 2
Name the two families of CDK inhibitors
CIP/KIP -- they have p21
INK4/ARF -- act on CDK4/CycD
The G2/M checkpoint is especially important in....
cells exposed to ionizing radiation
Two main mechanisms for altered expression of oncogenes following translocation
1. Swapping of gene regulatory elements to allow transcription of a quiescent gene
2. Formation of abnormal chimeric proteins
Chromosomal changes are especially associated with what kind of cancers?