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Exam 1
Lecture 2- Tumor Cell
87
Anatomy
10th Grade
01/26/2014

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Term
4 etiologies of cancer
Definition
gain DNa
lose DNA
change in nucleotide
epigenetic effect
Term
most tumors initally devlop as?
what happens over time?
Definition
monoclonal
get more aberattions->heterogentity/polyclonal
Term
non lethal genetic damage to _ initaties cancer?
what are these-4
Definition
cell regulation genes
DNA repair,
cell cycle,
cell signnaling/growth
apoptosis
Term
what are the protooncogenes-2
Definition
c-myc
Ras
Term
what are tumor suppression genes-2
Definition
p53
RB
Term
what are the genes that regulate cell cycle
Definition
CDk, cyclins
Term
what are the cell signal trnasduciton geneses
Definition
tyronsine kinase
Term
what % of cancers are inherited?
Definition
5-10%
Term
look at lside 5 for the heridiatry cancers
Definition
Term
to inherit breat cancer, a daughter gets a mutaiton in what gene?
Definition
BRCA 1 or 2
Term
what is BRCA fucniton?
Definition
DNA repair normally
Term
when a daughter gets the rbeast cancer mutation, its only 1 mutated and 1 normal alle. what happens over adolsesnce?
Definition
the other allele undergoes mutaiton to pave way for cancer in hormone tissues at early age
Term
Def:
ploidy
Definition
# of copies of chromosomes
Term
Def:
dilpoid
Definition
2 copies (1 chrom from dad and mom)
Term
Def:
polyploidy
Definition
mutlitple pairs of the chrom. beyond diploid set
Term
Def:
aneuploidy
Definition
cell has abnormal non-integer ploidy
Term
Def:
loss of heterozygoistiy
Definition
one chrom has normal allele and the toher has a mutant
Term
normally protoconocgenes do?
Definition
cell growth and proliferation
Term
in cancer cells what 2 gene splay majro role
Definition
protooncogene-> oncogene (++ growth_
tumor supression gene (is inhibited)
Term
this gene is the gas pedeal for cell proliferation
mutations cause-
Definition
proto-oncogene
break pedeal to stick- too much prolif (-> onco-genes)
Term
_ are the brakes for cell proliferation
mutation?
Definition
tumor supressor genes (negatively regulate)
brake failure- too muhc prolif
Term
Def:
oncogene
Definition
cancer causing dervied from proto-oncogene
Term
Def:
proto-oncogene
Definition
normal genes that promote cell prolfieration
Term
Def:
onco-proteins
Definition
proteins of oncogenes that resemble protooncogenes, but DONT need growth facotrs for production in transfromed cells
Term
Def:
protonco proteins
Definition
tell cells to grow/divide, but ONLY in response to signals (dont't listen to these signals when mutated)
Term
protooncogenes-> oncogenes results-4
Definition
overproduction growth factors
too many replication signals
uncontrolled stimulated in intermediary pathways
cell growth wiht increased trascription factors
Term
3 specific ways proto-oncogenes become oncogenes
Definition
deletion/point mutaitons
gene amplification
chromosome rearragnement
Term
cell protoncogenes can be mutated, captured by retrovirus, or have virus genes that mutate to oncogenes
Definition
Term
function of:
C-myc
Definition
transcription
Term
function of:
PDGF
Definition
growth factor
Term
function of:
CDK4
Definition
cyclin-dependent kinase
Term
function of:
Ras
Definition
signal transduction
Term
Cyclin D
Definition
cyclin binds to CDK4
Term
what is the chrom trnaslocaiton in Burkitt lymphoma?
result?
Definition
c-myc -> adjacnt IgG promoter
increased myc production
Term
what is the chromosome trnaslocaiton for leukemia
result?
Definition
Abl-> BCR locus (philedelphia chromosome)*
more potent tyrosine kinase activity
Term
slide 17 has the gene amplificaitons and the cancers caused
Definition
Term
example of molecular target therapy-
Definition
STI-571/gleevac/imatinib
Term
what is the MOA of gleevac/imatinib
Definition
molecule inhibts Bcr-Abl tyrosine kinase overexpressed
Term
what cancer does gleevac target
Definition
chronic myloid leukemia (refractory)
Term
what is the Ras inactive form?
active?
which is the mutation form always in?
Definition
GDP bound
GTP bound
GTP bound/active
Term
what is the function of ras?
Definition
transduces signals to stimulate proliferation
Term
*in tumor cells there is abornmal amt of EGFR (epidermal growth factor recpotrs)that signal cell proliferation
Definition
Term
EGFR does signal transductin thru what?
Definition
tyrosine phosphorylaiton
Term
when do EGFR and other like it not need ligand stimulation?
Definition
mutated cell form
Term
what molecules cna inhibit EGFR?-2
Definition
monclonal abs
small molecles
Term
what is the resting state in cell cycle?
Definition
G0
Term
what is hte DNA synthesis pjase of cell cycle?
Definition
S
Term
what is the sequcne for cell cycle?
Definition
G1->S->G2->M
Term
cyclin dependent kinases drive ht cell cycle, are the kinases active on their own?
Definition
no
Term
what are the CDK inhibitors that bind and inhibit the regulation of the cell cycle progresision?-2
Definition
p16
p21
Term
what is the CDK for G1-2
Definition
cdk4
cdk6
Term
that
Definition
Term
what CDK makes G1 go to S?
Definition
cyclin E, cdk3
Term
what CDK makes it go from S to G2?
Definition
cyclin A/CDK2
Term
what CDK makes it go from G2 to M?
Definition
cyclin B; CDK1
Term
what cell cycle check causes stop in S phase
Definition
unreplicated DNA
Term
what causes a cell cycle stop in the G2 phase
Definition
DNA damage
Term
what if after G2 the cell has high MPF?
Definition
goes to prophase
Term
what is the cell cycle check point that stops in M phase
Definition
improper spindle formation
Term
what if after M phase the cell has low anaphase inhibitor?
Definition
goes to anaphase
Term
what is the chekc point in G1 phase?
Definition
DNA damage
Term
deregulation of what is a hallmark of canceR?
Definition
cell cycle
Term
gene amplification of _ causes the cel cycle to progress faster?
Definition
CDKs (positve regulators)
Term
gene coding deletes/inhibits _ which causes cell cycle to go faster
Definition
CDK inhibitors
Term
the _ protiens are mutated in cancer so more dysregulation
Definition
checkpoint
Term
both or only one gene copy of a tumor supressor gene has to be defective to cause cancer
Definition
BOTH
Term
what are the tumor suppressor genes?-3
what cancer do each cause?
Definition
BRCA, P53, TGF-B
BRCA1=female, BRAC2= male and female breast
P53=most cancers
TGf-B: colon
Term
what is the gaurdian of the genome?
when is it activated?
Definition
p53
DNA damage
Term
MOa of P53
Definition
stops cell cycle if damage for repairs. if too excessive->cell death
Term
_ % of cancer have P53 mutaiton
if this mutation occurs ealy what happens?
Definition
50
more likely aggressive malginnancy
Term
what tumor supporessor protein control moving past G1 checkpoint to S?
Definition
retinoblastoma (rb)
Term
what is the MOA of Rb?
what happens when Rb is bound to it?
Definition
phosphylation in G1->rlease E2F transscirption facotrs. G2-> dephosy and binds E2f= stops DNa synth
-no trnascirption/replicaiton
Term
Rb is inactive when its phosphyrlated/dephosphyrlated? what cycline does this?
Definition
phosphyrlated
G1 CDK
Term
what is the consequcne of an inactive Rb
Definition
cells all go to S phase-> uncontrolled proliferaiotn-> cancer
Term
what is the rpocess of cell death that causes bursting into other areas and inflammatory?
what is the one where it just shrinks and disentrgrates inside the one membrane
Definition
necrosis
apoptosis
Term
chemo and radtion kill tumor cells how?
Definition
activaitng the orderly apoptotic pathways
Term
what is the anti-apoptotic/ prosurvivial gene?
Definition
Bcl2
Term
what is hte proapoptotic gene
Definition
Bax
Term
Bax nad Bcl2 are dimerizing proteins with _ domains
Definition
BH3
Term
pro and anti apoptotic genes are _ responsive
Definition
transcriptional
Term
_ modificaitons determine if apoptosis is active/inactive
Definition
post trnaslational
Term
activaiton of pre-apoptotic members may inovle?
Definition
trnaslocation
Term
balance btwn what 2 things determiens apooptosis or not?
Definition
BCL and Bax
Term
BCL 2 control the permability of-
these 2 protiens cause perambility to it thru channels or PTPs to allow apoptsis molecules
Definition
OMM (mitochondrial membrane)
Bax and Bak
Term
whcih pathway invovles stimulation of death receptors for apoptotiss
Definition
extrinsic
Term
whihc pathway for apoptosis incoled disruption of the mitochondiral permeaility releasing cytochrome C into cytoplasm
Definition
intrinisc
Term
in both pathways for apoptosis, _ are activaed and cell regulatory proetins are cleaved (by DNAase)
Definition
caspases (death proteases)
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