Lecture 26

Question 1

Hallmarks of cancer, what are they

Answer 1

Traits unique to cancer cell
-sustaining proliferation signalling (constantly maintaining GO signal even when medium doesnt support it)
-evading growth suppressors (like tumor suppressing genes)
-activating invasion and metastasis
-enabling replicative immortality (re-activating telomerase, can grow forever)
-inducing angiogenesis (BV proliferation)
-resisting cell death (apoptosis)

Question 2

How do originally normal cells develop the hallmarks of cancer

Answer 2

Through accumulated mutations, they add up and if they’re beneficial that will happen

Question 3

What’s one way in which cells sustain proliferation signalling

Answer 3

They no longer exhibit contact inhibition, 3T3 cells initially only grow on flat surfaces, not in suspension of fluid, therefore once the plate fills you done, but when cancerous they will continue growing to teh point of piling on top of each other

Question 4

What are the general groups of genes involved in cancer (groups of genes that when mutated may result in cancer

Answer 4

Onco gene: positive regulators driving tumouriogenesis (promoting growth)
Tumor suppressor genes: negative regulators (stopping growth)
DNA repair genes

Question 5

Onco vs proto oncogenes

Answer 5

Proto are the normal versions required for cell growth, necessary, and onco genes are the mutated, unregulated ones, the problematic ones

Question 6

Viral oncogenes

Answer 6

These come from viruses, they infect the cell, insert their RNA which is converted to cDNA, and this is then inserted randomly into the cells genome, so the host cell will be producing the viral DNA, in some cases it can be inserted right next to OG proto oncogene, and they will be transcribed together, this is how the virus causes unregulated levels of an oncogene product, resulting in the growth
This viral info is also highly subject to mutation

Question 7

V src

Answer 7

The onco version that can no longer autophosphorylate to inactivate itself, so its always, constitutively, active, leading to unregulated activity and cancer

Question 8

Viral promoters and cancer

Answer 8

Sometimes the viral promoter can be inserted right in front of the protooncogene, replacing its normal regulation, so now instead of being tightly regulated its just constantly in production

Question 9

What are the non-viral causes for changes in oncogenes

Answer 9

Mutation in coding sequence
Chromosomal abnormality (increased expression, fused genes, etc)

Question 10

What do RTKs do

Answer 10

Receptor tyrosine kinases
They sit on cell membrane and recognize growth factors, and in response the activate itself via phosphorylation, at tyrosine residues
Once self activated, adaptor proteins can bridge the receptors to the RAS GTP and activate it

Question 11

What does Ras do after being activated by RTK

Answer 11

It activates a kinase (Raf) that will go around phosphorylating another product that will continue a casacade, this resulting in the activation of a transcription factor that will initiate transcription of genes responsible for cell division

Question 12

Sos protein

Answer 12

Helps the conversion of RAS GDP to GTP, helps knock it off

Question 13

Onco gene Ras vs proto oncogene ras

Answer 13

Teh different between the normal and cancerous ras is in a point mutation that changed one amino acid that inactivated the hydrolyzing subunit of RAS, keeping it constitutively active, and if its always active is always doing its function, which is the activating of the cascade promoting cell growth, its no longer activated by RTK and the presence of growth factors, its just GOES

Question 14

Cause of Burkitt lymphoma

Answer 14

Translocation between chromosomes 8 and 14 affecting the proto oncogene c myc (TF that produced cellular growth)
What happens is the translocation keeps myc intact but not with its regulatory region, it gets paired with another regulatory region that results in its over expression, therefore excessive cell growth

Question 15

Chronic myeloid leukemia

Answer 15

Translocation between chromosome 9 and 22, fuses two genes, c-abl from ch 9, a kinase, and BCR on ch 22, result is a hyperactive kinase
C-abl controls cell suicide