Flashcards in neoplasia cancer 1 Deck (67):
proliferation in defiance of normal regulation
chemical that cuases cancer
where does cancer begin?
in a single cell clone
mutated gene intiating ccer
what triggers the process of cell-cycle
cell cycle control sysem
stages of cell cycle
s g2 m g1
where does cell cycle start
end of G to process to S phase
gap in the action
no DNA being synthesized and mitosis is not occuring
when is gap stages
between g2 and g1
what occurs during S phase
Dna and Histone synthesis
what regulates cell cycle stages
cyclins and cyclin-dependent kinases
what do cyclins do?
bind to and acivate cycline-dependent kinases
what happens to specific cyclins after phase
rapidly destroyed while cyclins for next phase are synthesized
what occurs in g1 phase?
protein synthesis and cells grow in size
checkpoint towards end of g1
determines if DNa after mitosis and everything else is ok to process
when do tumor supressors work?
Key regulation in cell cycle
specific cyclin in early g1 to turn on cell cycle and late g1 to turn on s-phase
how to convert a normal cell to a cancer cell?
more than one mutation is required
breats and colorectal multi-hit ex
9-11 mutatations per cancer cell
organization of dna in nuclei in eurkaryotes
what wraps dna in eucaryotes?
2 histones3, 2h4 2h2a 2h2b
how to regualte gene expression?
tightly wrapping DNA around nucelosomes
how to increase expression?
make RNA then protein
what does Ez do?
add 3 mh3 to h3k27
role of Ez
silencing some genes
news flash of Ez
increased in breast and prostate cancer
cancer that is due to mutations in an enzyme that methylates h3k4
how are epigenetic changes passed?
from daughter cell to duaghter cell
what does cancer always involve?
decreased tumor suppresor
increased activity of mutant protooncogenes
how is rtk activitated?
growth factor binds -->rtk dimerizes-->Activated RTK phosphorylates itself
what happens after phosp or rtk?
1. grb2.sem-5 binds to tyr on rtk via sh2 doman
2. binds to Sos & RAS via two SH3 domains
3. activates grf to exhnage ras bound gdp for GTP which makes RAS bind to RAF
3. RAF phosphorylates MEK-
4. MEK phosphorylates MAPK
5. mapk goes to nucleus phosphorylates FOS, Jun, MYo = turn on for growth
Ras GTPase activity occurs why?
from a GAP (gtpase activiating protein) that regulates growth activity of the pathway by inctiviated RAS
mutations leads to a loss of?
Ras GTPase activiate-->Ras is always on
mutations in myc or fos or jun can lead to ?
which transcriptions factor is common in many types of cancer?
how is P13 kinases activated?
by activated RTK by binding to one of those phosphotyrosines on an activiated RTK
what does Akt do?
promote growth and survival while inhbiting apopt.
what does akt stimulate
mTOR that stimlates protein sysnthesis in growing or surviving cells
what is capable of stopping P13 system
PTEN- regulator at first step
which cyclin starts the cell cycle G1?
which cyclin ends G1 phase?
how is the cell cycle rapidly turned on?
myc -->D-Cyclin-->phosphorylates Rb--->Rb comes of E2F-->E2F is active
what governs cell division to make more cells?
component in growth factor pathaways that promote growth
how do mitogens regulate cell division?
by their effects during the G1-phase of the cell cycle
what can cause unique retinal cancer
inheritred mutation of Rb protein that prevents it from binding to E2F proteins
what is increase expression of RB capable of?
regulate/stop cell division that is too rapid
1st way p53 works/
stimulates p21-->p21 binds to c-cdk g1/s and during s to prevent further progession
p53 response to dna damage
phosphorylated and prevents degradation. Blocks entry into M-phase and futher progresison of cell cycle
strongest way p53 works
stimulates programmed cell death
why would p53 levels increase
resonse to large increases in RAS and MYC that turn on cell
what can lead to a loss of function
mutaions in tumor repressors like P53
what prevents the formation of D-cyclin complex
what is persistent change in gene expression without a change in DNA sequence?
what happens if p16 is methylated?
turns of the expression of p16-->cancer
what happens if developmental genes are no longer silenced
breaking away from other cells in tumor to penetrate blood vessel or lymph vessel
metastiastic cells are resistant
to apoptosis and thrive independetly
what cuases angiognesis
hypoxia-->release of VEGF-->stimulate new growth of blood vessels
what drugs inhibits activit of vEGF
poster child for cancer drugd