Cancer I Flashcards
Cancer is a ____ disease, but other ____ changes also occur; what is it characterized by?
genetic; epigenetic; abnormal cellular growth and reduced cell death
How can cells accumulate DNA damage (2 ways)? List four targets of genetic damage
- Acquired (chemicals, radiation, viruses)
- Inherited in germ line;
- Growth promoting protooncogenes
- Tumor suppressor genes
- Genes regulating apoptosis or cell death
- Genes that repair damaged DNA
List the steps in which you can go from a normal colon to carcinoma?
- Germline or somatic mutations of cancer suppressor genes (first hit)
- Methylation abnormalities or inactivation of normal alleles (second hit)
- Protooncogene mutation
- Homozygous loss of additional cancer suppressor genes
- Additional mutations; gross chromosomal alterations
Where do tumors arise from? What else arises from original clone during continuous growth? How do these descendants differ from the original clone?
Single transformed clone;
new subclones arise from the original clone’s descendants;
Can be more aggressive, metastatic, and have ability to evade host defense
How many doublings are needed to get to 10^9 cells? What is the smallest clinically detectable mass? What is the max solid tumor mass that is compatible with life? How long woul it take to get a mass of 1 gm given this knowledge and the assumption that the cell cycle lasts 3 days?
30; 1 gm; 1 kg; 90 days (1 gm felt with 30 population doublings and 3 day cell cycle)
What are the two approaches to cancer treatment?
- Conventional chemo
2. Molecular Targeted Therapy
How do anticancer agents mediate their effects? How can these drugs act?
Induce cell cycle arrest and/or cell death; act in specific phase of cell cycle while others are phase nonspecific;
What is the cell cycle made up of (4 phases)? How much time could cells spend in these phases? What is Go?
G1, S, G2, M; 6-12 hr, 6-8 hr, 3-4 hr, 1 hr respectively; G0 has postmitotic cells exiting the cell cycle to enter a non-prolif phase (nerve cells) or some enter G0 temporarily and later re-enter the cycle
What proteins control the cell cycle progression (2)? What do these two combined help do? T/F: cdk’s can act on their own.
What does a cyclin determine?
- Cyclins (reg proteins, like A, B, D, E)
- Cdk’s (catalytic proteins, like 1, 2, 4, 6);
heterodimers that phosphorylate target proteins;
false: needs a cyclin associated to phosphorylate;
which proteins to be phosphorylated by cyclin-cdk complex
What are the cyclin-cdk complexes for G1, S, and G2/M phases?
Cdk4-cyclin D, Cdk2-cyclin A, Cdk1-cyclin B, respectively
What phosphorylates Rb? If it’s not phosphorylated, what happens with the thing it should be holding? What do progerssion from S to G2, and G2 to M involve?
Cyclin D/Cdk4, Cyclin D/Cdk6, Cyclin E/Cdk2; E2F is released and activates transcription of genes whose products control progression from G1 to S; cyclin A/Cdk2 and cyclin B/Cdk1
What are the four checkpoints in the cell cycle?
- G1 arrest: DNA damage, no progression to S (same with G2 going to M
- S-phase arrest: if DNA replication errors, no G2
- M arrest: If improper spindle formation, no division
What is a possible cause of breast cancer related to cdk/cyclin?
If cdks or cyclins overexpressed, cdks are hyperactivated (e.g. cyclin D and breast cancer)
How can a cell undergo apoptosis (two ways)?
Physiological process but can be induced
Morphological exam for apoptosis?
- cell shrinkage
- cell shape changes
- cytoplasmic condensation
- altered nuclear envelope, nuclear shrinkage
- chromatin condensation and fragmentation
- cell membrane blebbing
- formation of apoptotic bodies
- cell detachment
- phagocytosis of apoptotic bodies
