Cancer

Question 1

neoplasm

Answer 1

tumor-any abnnormal new grwoth of cell

Question 2

genetic basis of cancer

Answer 2

most cancer-causing mutatons are somatic

mutagens are mostly environmental

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

Question 3

Clonallyrelated cancer cells

Answer 3

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

accumulate aditional mutations-increase malignancy
-hetergenicty of cells

Question 4

Contact inhibition

Answer 4

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

-sto cells from prolifeating and migrating

Question 5

how loss of contact inhibition

Answer 5

loss of cadherins-break link to other cells

metallopretases0degrade ECM and facilitate tissue invaision

Question 6

g1/s transition

Answer 6

any pathwa that messes with this may cause cancer

Question 7

tumor supressor genes meaning and 2 typse

Answer 7

prevent tumor dev

• caretakeer-protein prevents damage or repairs DNA damage
• gatekeeper-induce apop or restain cell diviosn

Question 8

ocnogene

Answer 8

prteins promote cell growth and division

gain of funciton mutation leads to cancer-release of control

Question 9

tumor represor mutations

Answer 9

receissive-need to lose both copies
-loss of heterozygostiy

need loss of function to iactivate protein

appear domoinant in pedigrees

Question 10

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

Answer 10

MLH, BRCA, ERCC1

Rb and p53

Question 11

rb/p53 fucntions

Answer 11

rb-controls g1/s transition

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

Question 12

repair patway of MLH, ERCC1, BRCA1/2

Answer 12

MMR

NER-XP

DSBR-breast cancer

Question 13

two rb disease

Answer 13

sporadic-single tumors in one eye of one person

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

Question 14

Two hit hypothesis

Answer 14

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

bilateral-one even is required

Question 15

how to get loss of hetero

Answer 15

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

Question 16

p53 and cancer cells

Answer 16

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

Question 17

how to stimulate p53

Answer 17

DNA damage-protein kinases

growth factors-arf protin synthesis

Question 18

arf protein

Answer 18

alternative reading frames-transcribed from DNA that encodes CDK inhibitor

pro apoptotic

Question 19

MDM2

Answer 19

binds to ARF-destbilizes p53 since ARF cant stabilize

MDM2 is antiapoptotic

Question 20

p53 structure

Answer 20

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

Question 21

proto-oncogene

Answer 21

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

Question 22

two tyes of oncogene

Answer 22

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)

Question 23

cell cycle control pathway GF to end

Answer 23

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

Question 24

cell cycle control pathway tumor spupressor genes

Answer 24

NF1 (ras GAP)-supreses ras

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

Question 25

mTOR pathway, what are oncogenes or tumor sups

Answer 25

pip2-pip3-pkb-tsc-mTOR-protein synthesis/growth pip2 to 3-P13K pip3 t2-PTEN oncogenes-PKB, mTOR, P13K tumor sup-TSC, PTEN

Question 26

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

Answer 26

myc-overproduction abl-self activation-no need for normal reg stim ras-prevent inactivation

Question 27

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

Answer 27

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

Question 28

how t diagnose c-myc rpoblems

Answer 28

FISH see mny repeats-double minute chromasomes? also can see small dots where notmal should be

Question 29

c-myc disease

Answer 29

burkitt lymphoma tumor of b lymphoytes -powerful enchancer to make b lymphoytes translocate c-myc into hat region-much more trx

Question 30

c abl disease+ how diagnose+etiology

Answer 30

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)

Question 31

BCR

Answer 31

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

Question 32

c abl structure

Answer 32

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

Question 33

gleevec

Answer 33

binds to and stabilies inactive confomrmatin of c-abl

Question 34

oncogene addiction

Answer 34

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

Question 35

ras + GAP abilites

Answer 35

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

Question 36

GEF

Answer 36

replaces GDP by GTP

Question 37

GAP

Answer 37

gtpases-ras (intrinsicly) and NF1 switches GTP to GDP

Question 38

proteins with ras homology domain

Answer 38

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

Question 39

oncogenic mutation in ras

Answer 39

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