Cell Cycle pt. 2 Flashcards
tumors
lesions that may or may not be neoplasms
neoplasms
abnormal growth with abnormal regulation, benign or malignant
cancer
malignant neoplasm
metastasis
secondary growth of cancer at a different location
initiation of carcinogenesis
simple mutation in one or more genes that control key regulatory pathways of cells
genotitic even (change in DNA sequence)
Promotion of carcionigenesis
selective functional enhancement of signal transduction pathways that were induced by initiator by continous exposure
epigenetic event, change in gene regulation
Progression of carcinogenesis
continuiing change of the basically unstable karyotype
clastogenic event
Things to know about initiation
irreversible
no threshold
caused by chemicals, radiation, ROS, viruses
change in cellular DNA
single mutation, chromosomal translocation, gene amplification
can lead to activation of onocogenes and inactivation of tumor supressor genes
Things to know about promotion
occurs over long span of time
reversibly in early stages, lifestyle changes may prevent
involves gene activation or repression such that latent phenotyp of intiated cell becomes expressed through cellular selection and clonal expansion
there is a threshold
can inhibit cell death of initiated cells
monoclonal tumors
come from one type of cell
polyclonal tumors come from
many typs of cells
Things to know about progression
complex genetic changes
irreversible gene expression changes
evolution of karyotypic instability
selection for optimal growth in repsonse to cellualr environment
results in the conversion of benign tumors to malignat ones and maybe metastasis
Cancer cells evade death by
being self sufficient, using growth signals, becoming insensitive to inhibitory signals, acquire limitiless replcaition potential, avoid immunology, promote inflamation, reprogram metabolism, sustain angiogenesis, so cool
oncogenes
cellular genes that stimulate cell division and/or growth
loss of regulation can lead to enhanced expression of these proteins and tell the cell “Divide! Divide!” (unregulated cell division and growth)
tumor supressors
cellular genes that serve to check or inhibit cell division
loss of expression of these proteins leads to cell growth or cell division
oncogenes are always
dominant mutations/overexpressions
they result from a gain of function mitation
only one of the two alleles needs to be activated for it to affect cell
rarely in germline inheritance
Three forms of oncogenes
cellular proto-oncogenes that have been captured by retrovirus
virus specific genes that behave like cellular proto-oncogenes that have been mutated
cellular proto-oncogenes that have been mutated
Raus Sarcoma
chicken
src oncogene
non-receptor TK
colon carcinoma
oncogeneic element in type 1 transducing viruses
cellular oncogene carred in retrovirus
basically, when retroviruses go into cellular DNA, they leave and take oncogenes with them
oncogenic element in type 2 non-transducing viruses
cellular oncogene activated by proviral insertion/integration
basically, virus goes into genome and changes promoter (oncogenese can be promoted)
oncogenic element in type 3 non-transducing long latency viruses
retroviral transactivating protein disrupting normal regulation of cellular transcription
retrovirus activates disrupting DNA (?)
oncogenic element in type 4 retroviruses that contain an envelope that signal
inappropriate cellular signaling resulting from viral enveleop/cell receptor interactions
acts like a mitogen
conversion of protooncogenes to oncogenes: truncatoin
loss of regulatory domain
product is over active
conversion of protonocogenes to oncogenes: point mutation
in coding region-unregulated product
in promoter or enhancer-overproduced
conversion of protooncogenes to oncogenes: insertion
viral promoter or enhancer-overprocued product
conversion of protooncogenes to oncogenes: gene amplification
amplifies DNA, overproduced product
conversion of protooncogenes to oncogenes: translocation
to a strong enhancer-overproduced product
with gene fusion-fusion with protein with abnormal properties
growth factor oncogenes
PDGF
EGF
M-CSF
GTP bining proteins oncogenes
ras
transcription factors oncogenes
myc
fos
jun
TR, RAR
too much myc or ras and the cell
will continue dividing!
k-ras
chrom: 12p12.1
cancers: lung, ovarian, colorectal, bladder, carcinomas (5-20%)
protein: small G protein
N-ras
chrom: 1p13
cancers: head and neck cancers (30%)
protein: small G protein
H-ras
chrom: 11p15
cancers: colorectal cancers
protein: small G protein
c-myc
chrom: 8q24
cancers: various leukemias, carcinomas (10-50%)
protein: TF
L-myc
chrom: 1p32
cancers: lung cancer
protein: TF
Tumor Supressor Genes
recessive
repress gorwth
inactivating mutations, deletions, loss of expression=carcinogenesis
germline inheritance frequent in cancer development
no known virus involvement
Types of tumor suppressor genes
p53, Rb, p16/ink4a (p53 controls ccc in G1 and G2, mutated lose control of division)
all proteins are cell cycle regulatory proteins
P16/INK4A
many studies show inactivation of the ink4a locus on chromsome 9p21 in cancers
2nd most common inactivated gene
via gene mutation, deletion, CpG island methylation in promoter region
Rb (retinoblastoma)
not limited to loss of both allele to cause Rb
Rb is the gaurdian of the restriction point
can be genetic loss or other reasons
inactivation of Rb gene by mutation
retinoblastoma, osteosarcoma, small cell lung carcinoma
methylation of Rb gene promoter
brain tumors, others
sequestration of pRb by Id1, Id2
diverse carcinomas, neuroblastoma, melanoma
sequestration of pRb by the HPV e7 viral oncoprotein
cervical carcinoma
cancer needs several ___ for cancer to result
mutations in several gene products or genes
