#30 Cancer Flashcards Preview

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Flashcards in #30 Cancer Deck (52):
1

What gets activated by bcr/abl in CML?

the c-able protooncogene encodes a prtoein tyrosine kinase that helps control cell proliferation

proto-oncogene is specially altered at the break point in both Burkitt's and CML of these chormosomal translocation

2

what is sis oncogene?

Secreted Growth factor

in Platelet derived growth factor

3

what is erbB?

located in PM

epidermal growth factor recetptor (truncated)

4

Waht is erbA?

nuclear


thyroid hormone receptor

5

What is src oncogene?

rous avian sarcoma in cytoplasm

PROTEIN TYRSOINE KINASE that phosphoryaltes tyrosine residues

6

what is abl?

animal retrovirus (jbelson murine leukemia)

and nonviral tumor (CML)

cytoplasm and nucleus

protein kinase

7

what is Ha-ras>

animal retrovirus-harvey murine sarcoma

nonviral tumor- bladder, mammary, skin

plasma memebrane

Guanine nucleoide (GTP) bindign protein with GTPase activity

8

myc

animal retrovirus- avian myeloctamosus

nucleus

transcription factor

9

what is Rb?

nonviral tumor- retinobastoma and osteosarcome

nucleus

transcciption factor
tumore suppressor protein

(anti oncogenes

10

what is p53

nonviral tumor - most types of human cancer

nucleus

tumor suppressor proetins (anti-oncogenes)

11

what are teh two tumor suppressors we learned about?

p53
rb

12

what are four modes of intercellular signaling

1endocrine- hormone into blood

2. paracrine- secretory ecll to adjacent target cell


3. Autocrine- target sites on secreteory cell

4. Juxtacrine- signaling cell to adjeance ttarget cell via cell surface proteins

13

What are two general classes of hormones and NTs?

1. lipoholic with intracellular receptors (steroid, thryoxine, retinoids)


2. soluble (H20) with PM receptors
generate 2nd messnegers, GTP coupled epi, glucagon, serotonin< enzymeatic activity (try kinase)
receptor interacts with enzme

reeptor is an ion channel

14

What are downstream effects of Hormones and NTs

1. effect on enzyms in metabolic pathways
cAMP--> PKA --> glycogen

2. Effect on enzyme controlling cell scyle and cell division

EGFR--> Ras --> MAP kinase --> Rb, P53, Cdk, etc


effects on nuclear events, particualrly transcription
EGFR--> Ras --> Raf --> MAP kinase --> SRF --> SRE

effect

15

Growth factor singal transduction pathway

GF--> GFR --> P I3 Kinase (inosital) --> protein kinase activation --> active eIF4E or phopshoryted S6 kinase --> incerased mRNA translation --> sitmulation of cell growth

16

mitogen signal pathway

migoten --> mitogen cell rR --> act RAS --> MAP kinase --> myc gene transcribes Myc

17

What is p21 RAS

key regulator of intracellular signaling pathwya and contributing factor in many cancers

mutated in 30% of cancers

g protein or GTP-bidningprotein- active when GTP is bound0 inactive when GDP is bound

GTPase activity- slowly hyrolyzes bound GTP to GDP --> self inactivates

18

what are Ras and Myc

two oncogenes

19

mutation of two oncogens is more lethal than one

yep

20

What are the minimum requirements for teh transformation of human cells

1. telomerase (prevent telomer shortenting) (hTERT telomerase catalytic subunit)

2. large T-antigen (SV40) - hits Rb and p53

3. Ras

21

what are th minimum requiremnts for transormation of rodent cells

Ras

T antigen (SV40) or myc

22

What are the DIRECT gene/processes that functions under myc oncogene?

1. cyclin D

2 SCF subunit

3. E2F

23

What are the indirect gene/processes that function under myc oncogene

1. C1-Cdk

2. Degradatin of p27 (inhitibor of porliferation)

3. G1/S-CdK activation- via Rb phosphorylation

4. increased E2F activity, via phosphorylation

5. S-phase entry- via above mehcanism

24

how does a normal cell respond to excess myc?

induceds cell cycle arrest or apoptosis

25

how does an abnormal cell respond to excess myc?

will further inactivate p53 leading to a tumor

26

What is the dosage hypotheses (ways proto oncogene can be converted into an oncogene)

celular ongene directs sytnehssis of an amt of a normal protein produt tha tis required for nomral growth and that transofmraiton to cancerous growht results form overproduciton of noamrl protein

tumor retrovirus, overproduciton may be directed by viral oncgoene uner viral control

27

what is the mutationtal therory of goinf rom proto-oncogene to oncogen

gene product fro oncogene is differnt form gene product form proto oncogene

differnec ein aa sequene is thought to lead to unregulated activity or othrwise abnromal actiity

ras gene and src gene

28

what causes colorectal cancer?

K=ras mutations

29

how does cetuximab medicaion help with K-ras colorectal cancer mutations

cetuximab is anbitody directected toward EGF R

patients with tumor beairn mutated K-ras DOES NOT benefit from cetuximab

patiens with tumor bearing wilt type K-ras DID benegift form cetuximab

30

what is Her 2 Receptor --> Neu

conversion of native protein to hyperactive oncoprotein by mutatino (ligand dependent proto-oncogene receptor proteins)

Val --> Gln in TM

31

difference between formation of tumor from proto-ocncogene vs tumor suppressor gene

Proto-oncogenen (accelerator) - only need ONE mutatuion to be overexpressed to cause cancer

Tumor suppressor gene (brakes) - need mutaiton in BOTH copies to be inactivated

32

What are the six hot spot residues of p53

R249
R248
R273
R282
G245
R175

33

which hot spots direclty ontact DNA (while the others are necessary for integrit of structurla elements?

R 248
R 273

34

What does HPV cause? what causes HPV

warts and cervical cancer

virus induced cancer, p53 and environtmentm

35

molecular biology of HPV induction of cancery

by inactivation of P53 and Rb through

p53 inactivated thorugh E6 oncoprotein
Rb inactivated by E7

36

what is Arg/Pro 72

common polymorphism in p53

R72 is more susceptible to E6 indueced degradation

37

do paitents with HPV ass. tumors have R72?

yes

38

how many more time susceptila is a patient with arg 72 to have HPV-associated tumorigenesis than heterozyge?

7x more susceptible to HPV

39

what are capsases?

protease invovled in the apoptotic process

ultimately proteoglyze a large specific set of downstream proteins and enzymes, activating some and inactivating others

40

what inititatates P53 for directing apoptosies

1. killer cells in immune system
2. UV light
3. intrinsic inducement form damage to mitochondria by reactive ROS or canges in membrane ptoenttial that lead to relase of cytoscome

dowstream events lead to activation of capase cased

41

what are caspases

aspartyl cysteinyl proteases that exist in a proform that can be proteolyzed to active caspase form

activation of endonucleases lead to framentation of DNA into discrete sizes

42

apoptosis from outside (cell extrincic pathway)

killer T cells --> assembly of DISC --> activatino and cleavage of procaspase 8, 10 or both -> apoptotic target cells

43

apoptosis from inside (intrincisc pathway

relese of cyt c (apoptotic stimulatou --> act by aparf 1 --> CARD domain --> apoptosome --> recrutiment of act of procasase 9 --> caspase 9 cleaves and thereby activates executional procaspases

44

what stimulates extrinsic apoptosis 2

1. killer cell
2. trohic support removal

45

what are players of extrinsic apoptosis 3

1. Fas lignad
2. Fas reeptor
3. DISC

46

What is initatior Caspase

caspase 8/10

47

what is executionaer caspase

caspase 3

48

what is intrinsic stimulus for apotposis

1. DNA Damage
2. Mitochondrial damage (memrane potential loss , ROS)

49

what are players for intrinsic apptosis

Cyt c
apaf 1, apoptsome
Bcl12 (ant, bax, bad (pro

50

what is initiator caspase intrisncic

caspase 9

51

what is execulationar capsas

caspase 3

52

difference between apoptosis and Autophagy

autophagy
lack chromatin condensation
lack DNA ladders
amssive cacualization of cytoplasm
accumulation ofdouble membrane autophagic vacuoles
little or no uptake by phagocytic cells, in vivo