Flashcards in #30 Cancer Deck (52):
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
what is sis oncogene?
Secreted Growth factor
in Platelet derived growth factor
what is erbB?
located in PM
epidermal growth factor recetptor (truncated)
Waht is erbA?
thyroid hormone receptor
What is src oncogene?
rous avian sarcoma in cytoplasm
PROTEIN TYRSOINE KINASE that phosphoryaltes tyrosine residues
what is abl?
animal retrovirus (jbelson murine leukemia)
and nonviral tumor (CML)
cytoplasm and nucleus
what is Ha-ras>
animal retrovirus-harvey murine sarcoma
nonviral tumor- bladder, mammary, skin
Guanine nucleoide (GTP) bindign protein with GTPase activity
animal retrovirus- avian myeloctamosus
what is Rb?
nonviral tumor- retinobastoma and osteosarcome
tumore suppressor protein
what is p53
nonviral tumor - most types of human cancer
tumor suppressor proetins (anti-oncogenes)
what are teh two tumor suppressors we learned about?
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
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
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
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
mitogen signal pathway
migoten --> mitogen cell rR --> act RAS --> MAP kinase --> myc gene transcribes Myc
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
what are Ras and Myc
mutation of two oncogens is more lethal than one
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
what are th minimum requiremnts for transormation of rodent cells
T antigen (SV40) or myc
What are the DIRECT gene/processes that functions under myc oncogene?
1. cyclin D
2 SCF subunit
What are the indirect gene/processes that function under myc oncogene
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
how does a normal cell respond to excess myc?
induceds cell cycle arrest or apoptosis
how does an abnormal cell respond to excess myc?
will further inactivate p53 leading to a tumor
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
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
what causes colorectal cancer?
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
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
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
What are the six hot spot residues of p53
which hot spots direclty ontact DNA (while the others are necessary for integrit of structurla elements?
What does HPV cause? what causes HPV
warts and cervical cancer
virus induced cancer, p53 and environtmentm
molecular biology of HPV induction of cancery
by inactivation of P53 and Rb through
p53 inactivated thorugh E6 oncoprotein
Rb inactivated by E7
what is Arg/Pro 72
common polymorphism in p53
R72 is more susceptible to E6 indueced degradation
do paitents with HPV ass. tumors have R72?
how many more time susceptila is a patient with arg 72 to have HPV-associated tumorigenesis than heterozyge?
7x more susceptible to HPV
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
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
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
apoptosis from outside (cell extrincic pathway)
killer T cells --> assembly of DISC --> activatino and cleavage of procaspase 8, 10 or both -> apoptotic target cells
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
what stimulates extrinsic apoptosis 2
1. killer cell
2. trohic support removal
what are players of extrinsic apoptosis 3
1. Fas lignad
2. Fas reeptor
What is initatior Caspase
what is executionaer caspase
what is intrinsic stimulus for apotposis
1. DNA Damage
2. Mitochondrial damage (memrane potential loss , ROS)
what are players for intrinsic apptosis
apaf 1, apoptsome
Bcl12 (ant, bax, bad (pro
what is initiator caspase intrisncic
what is execulationar capsas