lecture 35

Question 1

every hour in 2023 =

Answer 1

27 canadians expected to be diagnosed with cancer

Question 2

which cancer causes most deaths

Answer 2

lung cancer

Question 3

describe cancer death rates over the years

Answer 3

have decreased
early detection important - before metastasis

Question 4

name hallmarks of cancer - 6

Answer 4

sustaining proliferative signalling
evading growth suppressors
activating invasion and metastasis
enabling replicative immortality
inducing angiogenesis
resisting cell death

Question 5

describe ex of sustaining proliferative signals/evading growth inhibition

Answer 5

normal 3t3 (divide 3 times in day) cells = fibroblasts
transformed 3t3 cells = diff shape and can grow on top of each other = bECAUSE src oncogene transforms normal cells to become insensitive to contact inhibition

Question 6

can cancer be a genetic disease

Answer 6

yupppp
syndromes can be inherited

Question 7

name the cancers that can be genetically tested for and th genes they look at

Answer 7

hereditary breast cancer and ovarian cancer syndrome = BRCA1, BRCA2
li-fraumeni syndrome = p53
familial adenomatous polyposis = apc
retinoblastoma = rb1
ALLL tsgs

Question 8

what are oncogenes

Answer 8

positive regulators driving tumorigenesis = becomes hyperactive

Question 9

what are tumour suppressor genes - tsgs

Answer 9

negative regulators that are inactivated in cancer= loss of function mutations

Question 10

what are dna repair genes

Answer 10

prevents mutations maintain dna integrity = maintenance

Question 11

describe tumor virus - rous sarcoma

Answer 11

chicken with sarcoma - removed - grind up - filter - inject to another chicken = now has sarcoma
1910 = peyton rous discovered particles smaller than bacteria could reproducibly induce sarcomas in chickens = led to discovery of tumor virus - rna tumour virus
virus must carry a cancer causing gene

Question 12

what was first oncogene

Answer 12

v-src = isolated from rous sarcoma - 1970

Question 13

what are protooncogenes

Answer 13

required for normal cellular function but when mutated become oncogenes and promote cancer formation
like when incorporated into viral genome

Question 13

describe discovery of proto oncogene

Answer 13

late 1970s = search for related sequences in normal cells and discovered proto oncogenes - c src

Question 14

describe whole process of viral oncogenes - transcription

Answer 14

retrovirus inserts into cell - reverse transcription and inserts into host chromosome next to proto onco
then provirus makes mistake and transcribes protoonco = c src = now protoonco incorporated into virus
in v src - c term of protein responsible for neg regulation is absent
in repeated rounds of viral infection = proto oncogene becomes rearranged or mutated or both
= produced oncogene = now inserted back into host chromosome
Promotes cancer formation when expressed in normal cells

Question 15

describe whole process of viral oncogenes - expression

Answer 15

retrovirus infects a cell = provirus inserts near a proto oncogene = strong viral promoter stimulates overexpression of proto oncogene = bad

Question 16

describe non-Viral transformation of proto- oncogenes to oncogenes

Answer 16

in humans = most proto onco genes activated in absence of viral infection = by

mutations in coding sequences and chromosome abnormalities (increased expression or fusion protein that is a cancer specific form)

Question 16

what is RTK

Answer 16

receptor tyrosine kinase = cell surface proteins that bind to extracellular signalling molecules like growth factors
binding of singling molecule = leads to phosphorylation on tyrosine residues
ex - activated ras - adaptor molecules bind to receptor and link to ras, ras binds gtp and is activated

Question 17

describe ras more

Answer 17

gtp bound ras binds raf (kinase) = initiates cascade of phosphorylation events
raf - activates mek and that activates map and then map activated tfs
activates transcription factors that promote growth

Question 18

describe ras in normal cells

Answer 18

Carefully controlled
sos = gef = stimulated gdp–> gtp exchange = turns on and activates downstream ser/threo kinase
ITS A SELF TIMER
Intrinsic gtpase activity = turns it off

Question 19

what happens if single point mutation in ras

Answer 19

enough to drive tumorigenesis
ex = GGC –> GTC = gly to val = now gets stuck in active form
ras wild type to ras oncogene

Question 20

describe oncogenic activation of ras

Answer 20

ras g12v mutation = promotes growth and cascade with no growth signal

Question 21

are oncogenes dominant

Answer 21

mutant alleles - oncogenes tend to be dom = one copu of mutant allele enough to induce excessive cell proliferation
mutation in single cell - NOT every cells in organism = still leads to tumour

Question 22

describe burkitt lymphoma (b cell) cancer

Answer 22

reciprocal translocation between chrom 8 and 14 = t(8:14)

Question 23

what is c myc

Answer 23

tf whose normal function is to promote cellular growth/proliferation = proto oncogene
transcription tightly regulated = only on when needed

Question 24

what happens to c myc in burkitt lymphoma

Answer 24

myc is translocated so there is a regIG strong promoter near it = now myc is hyperactive
coding sequence of myc not changed
but myc is overexpressed by ig regulatory elements

Question 25

describe CML - chronic myelogenous leukemia

Answer 25

reciprocal translocation frequently seen in cml
Philadelphia chromosome t(9:22) is observed in 95% of ppl with cml

Question 26

what is c-abl

Answer 26

protein kinase involved in many cellular processes (proto-oncogene)

Question 27

describe c-able - cml

Answer 27

causes new protein - affects coding sequences
chimeric protein at molecular level
Recombines and makes brc1-able fusion protein = now new protein
brc1-abl becomes hyperactivated kinase
medicated to target fusion protein = gleevec