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Flashcards in Cancer Deck (39):
1

neoplasm

tumor-any abnnormal new grwoth of cell

2

genetic basis of cancer

most cancer-causing mutatons are somatic

mutagens are mostly environmental

Need mutliple mutations in many pathways
-major target is cell diviosn

3

Clonallyrelated cancer cells

all tumors begin with single cell-increase in size as population of tumor cells grow

accumulate aditional mutations-increase malignancy
-hetergenicty of cells

4

Contact inhibition

cells lose thjier abilty to respond to ECM and neighboring cell signals

-sto cells from prolifeating and migrating

5

how loss of contact inhibition

loss of cadherins-break link to other cells

metallopretases0degrade ECM and facilitate tissue invaision

6

g1/s transition

any pathwa that messes with this may cause cancer

7

tumor supressor genes meaning and 2 typse

prevent tumor dev
-caretakeer-protein prevents damage or repairs DNA damage
-gatekeeper-induce apop or restain cell diviosn

8

ocnogene

prteins promote cell growth and division

gain of funciton mutation leads to cancer-release of control

9

tumor represor mutations

receissive-need to lose both copies
-loss of heterozygostiy

need loss of function to iactivate protein

appear domoinant in pedigrees

10

exmaples of caretakes (3) and gat keeper (2)

MLH, BRCA, ERCC1

Rb and p53

11

rb/p53 fucntions

rb-controls g1/s transition

-53 halts cell di]viosn/initatse apoptosis in response to DNA stress

12

repair patway of MLH, ERCC1, BRCA1/2

MMR

NER-XP

DSBR-breast cancer

13

two rb disease

sporadic-single tumors in one eye of one person

familial-usually bilateral tumors (possibly multiple in one young). younger age, multiple family members affected

14

Two hit hypothesis

unilateral tumor-expected if two events needed for tumorto start forming
-loss of heterozygosity

bilateral-one even is required

15

how to get loss of hetero

chrom loss, duplicaton, mitotic recomb, gene conversion, deletion, epigentic, etc

16

p53 and cancer cells

loss of p53 renders cancercells immun toapop

stimulate trx of factors that block cell cycle (CDK inhibs/pro apoptotic proteins)

Converence point for many pathways

17

how to stimulate p53

DNA damage-protein kinases

growth factors-arf protin synthesis

18

arf protein

alternative reading frames-transcribed from DNA that encodes CDK inhibitor

pro apoptotic

19

MDM2

binds to ARF-destbilizes p53 since ARF cant stabilize

MDM2 is antiapoptotic

20

p53 structure

p53 is intriniscally unstable-stablized by DNA damage
-no inherent tertiary structure
-oncgogenic mutations can block DNA binding domain
-drugs are used to stablize p53

21

proto-oncogene

normal gene that can trn into an oncogene as result of mutations or increased expression

22

two tyes of oncogene

viral-v-src-get DNA from cell, mutate it, put into another cell

cellulr oncogene-leads to continuous activity of protin GOF (dominant)-or LOF (recessive)

23

cell cycle control pathway GF to end

growth facotors
GFR-TK
ras
protein kinase cascade
TF's
cyclin and cdk-inhibits RB
Rb-inhibits nex step-
E2F/G1/S

all of ones where not inhiibited-stimulate next step

all of these except RB and G1/S are oncogenes

obviously many places for mutaions

24

cell cycle control pathway tumor spupressor genes

NF1 (ras GAP)-supreses ras

TGfbeta-TGFbeta receptors-TF-CDK inhibtor
-inhbits CDK

25

mTOR pathway, what are oncogenes or tumor sups

pip2-pip3-pkb-tsc-mTOR-protein synthesis/growth
pip2 to 3-P13K
pip3 t2-PTEN

oncogenes-PKB, mTOR, P13K
tumor sup-TSC, PTEN

26

activaton of c-myc, c-abl, c-ras

myc-overproduction

abl-self activation-no need for normal reg stim

ras-prevent inactivation

27

c-myc what it does and how mutation occurs that leads to problem

stimulate cell cycle
-amplified in many tumor

number of copies can be increased (gene amplification) and chromasmal translocation can occur-put in front of srong promoer

28

how t diagnose c-myc rpoblems

FISH

see mny repeats-double minute chromasomes?

also can see small dots where notmal should be

29

c-myc disease

burkitt lymphoma

tumor of b lymphoytes
-powerful enchancer to make b lymphoytes

translocate c-myc into hat region-much more trx

30

c abl disease+ how diagnose+etiology

CML

philidelphia chromasome

translocation of 9 to 12, small p[art of 22 breaks off (philidelphia)-other part goes onto chromaosme 9
-attaches behind BCR-no more protein kinase to turn on (contintuivilty active)

31

BCR

breakpint cluster reion-on chromasome 22
-creates protein that does nto have to be activated

32

c abl structure

sh-src homology-oncogene withprotein kinase activity

sh2/3-regulatory-inhibit kinase untl they are modifed by activatd inhibitor

sh1-portien kinase domain

activation loop-poly peptidee chain in sh1 domain that occludes active site-can be phophorylated toallow substrateto bind
------add 2 oligomerzed bcr in front-activate kinase that can do whatever it wants now

33

gleevec

binds to and stabilies inactive confomrmatin of c-abl

34

oncogene addiction

glevec

main component of cancer driving pathay makes a bottleneck-this gene becomes the king becuase others are gotten rid of because this one is the best for abnromal environemt-target this gene

35

ras + GAP abilites

active when bound t GTP, inactive at GDP
-two gap actvites (intrinsic and extrenisc by GAPs (like NF1)
-intrinsic is not as effecient as GAPs
-need both to ensure ras sigals properly

36

GEF

replaces GDP by GTP

37

GAP

gtpases-ras (intrinsicly) and NF1

switches GTP to GDP

38

proteins with ras homology domain

alot-results in cell growh, cell adheion, ant apop, membrane traffic, etc.

39

oncogenic mutation in ras

gly 12 and gln 61
0reudece GAP (gtpase) activty of ras
0spends more time active