Carcinogenesis I Flashcards
The RB protein is hyperphosphorylated in rapidly proliferating cells at ____ of the cell cycle.
S or G2
__________ and _________ may activate oncogenes or inactivate tumor suppressors.
Translocations; gene deletions
Autosomal recessively inherited cancers are? (4)
1) xeroderma pigmentosa (XP) 2) ataxia-telangiectasia (AT) 3) Bloom’s syndrome 4) Fanconi’s congenital aplastic anemia (FA)
Burkitt lymphoma
a cancer of B lymphocytes found in the germinal center
____ correlates with a poor prognosis in many cancers.
Aneuploidy
Cancer cell phenotype: _________: lack many of the specialized structures and functions of the tissue in which they grow.
de-differentiated
Chronic myelocyctic leukemia (CML) is associated with _________ and also see ________.
the Philadelphia chromosome; Burkitt lymphoma
xeroderma pigmentosa (XP)
ability to repair UV damaged DNA is deficient; cancers occur even after very minimal sun exposure
What binds to and inactivates the mutant RB protein?
1) SV40 T antigen 2) HPV E7 protein
What happens to oncogenes in carcinogenesis?
they are activated
Cancer cell phenotype: ________ : capable of shedding cells that can drift through the circulation and proliferate in other sites.
metastatic
What is the hallmark of the antioncogene or tumor suppressor gene?
tumor results from a single cell that has acquired homozygosity
Name 2 tumor suppressors tumors that function by LOH.
1) retinoblastoma (RB) 2) APC gene in FAP
A _______ is made up of cells that are not invasive or metatstatic, but they have lost ______. They are _____.
benign tumor; growth control and functions of normal cells; immortal
When there is no RB or when it is nonfunctional, cells cannot ______ and _____.
down regulate the cell cycle; grow out of control
_____ by CDKs inactivate the RB protein, therefore allowing the cell to proceed from G1 to S.
Phosphorylation
Cancer cell phenotype: _________: capable of outgrowth into neighboring normal tissues to extend the boundaries of the tumor.
invasive
Early in life, _______ in somatic cells will produce ____ many years later.
mutagenic events; tumors
Inactivation of tumor suppressors may occur by ____.
LOH
What happens to anti-oncogenes/tumor suppressors in carcinogenesis?
they are inactivated
What is ataxia-telangiectasia?
severe neuro disability coupled with small dilated blood vessels and increased risk of lymphomas and leukemia
The RB protein is a target for animal tumor viruses, such as ______ and _____.
SV40 and HPV
What is loss of heterozygosity?
gross chromosomal event that results in the loss of entire genes and the surrounding chromosomal region
What does XP stand for?
xeroderma pigmentosa
What does AT stand for?
ataxia-telangiectasia
What is the second hit?
deletion of the second, functional allele
If E7 and E6 expression is blocked, ______.
the cells return to normal phenotype
The RB protein is hypophosphorylated in _____ cells in G0.
non-proliferating
Autosomal dominantly inherited cancers are? (4)
1) familial adenomatous polyposis (FAP-APC) 2) familial retinoblastoma (RB) 3) familial breast and ovarian cancer (BRCA1 and BRCA2) 4) Wilms tumor syndrome
Aneuploidy
the wrong # of chromosomes
Name the 2 types of genes that allow tumor initiation.
1) oncogenes 2) anti-oncogenes/tumor suppressors
Cells derived from a high frequency of _____ and from ______ carry a defect in the RB gene.
small cell lung cancers; some breast tumors
Philadelphia chromosome
chromosomal abnormality from a 9;22 translocation
Persons who survive inherited RB have an increased risk of ______, which is usually ______ in origin.
developing a 2nd neoplasm; mesenchymal
Name 4 steps in carcinogenesis.
1) tumor initiation 2) promotion 3) conversion 4) progression
What inhibits p53?
E6 protein
What is an example of a mutagenic event presenting its effects years later?
UV light exposure develops melanoma later in life
The RB protein is a target for ______.
animal tumor viruses
____ cells have been growing for 60 years.
HeLa
Tumor initiation occurs by mutations in at least ______.
2 types of genes
Because RB is an inhibitor of cell proliferation, it is ____.
an anti-oncogene or tumor suppressor
The RB protein is __________ in rapidly proliferating cells at S or G2 of the cell cycle.
hyperphosphorylated
Phosphorylation by ____ inactivate the RB protein, therefore allowing the cell to proceed from G1 to S.
CDKs
What is familial adenomatous polyposis?
polyps in the large intestine that turn into cancer if left alone
________ is inherited.
Susceptibility to cancer
What is the incidence rate of RB?
1:20,000
Cancer cell phenotype: __________: derived from a single cell.
clonal
______ is associated with the Philadelphia chromosome and also see Burkitt lymphoma.
Chronic myelocyctic leukemia (CML)
HeLa cells express _____ and ______.
HPV E7 and E6 protein
Name 3 DNA repair genes.
1) p53 2) BRCA1 3) BRCA2
If _______, the cells return to normal phenotype.
E7 and E6 are blocked
Sporadic cases of RB have _____ retinoblastoma while inherited cases are _____.
unilateral; bilateral
The Knudson theory states that ____ are needed to produce _____.
two; retinoblastoma
What is the first hit?
a point mutation in one gene
How do SV40 and HPV work?
they drive a quiescent cell into the S phase to proliferate and produce the viral protein
Cancer is related to the accumulation of ______ produced by ______.
somatic mutations; environmental factors
In RB -/- mice, loss of RB results in _____.
pituitary tumors with 100% penetrance
The RB protein is ______ in non-proliferating cells in G0.
hypophosphorylated
A mutation in a _______ increases the rate of obtaining further mutations.
DNA repair gene
Phosphorylation by CDKs _____, therefore allowing the cell to proceed from G1 to S.
inactivate the RB protein
anti-oncogenes/tumor suppressor genes
inhibit cellular proliferation
Cancer cell phenotype: _____ to normal signals for proliferation control.
unresponsive
Susceptibility to cancer can be inherited in a _____ or ____ manner.
dominant; recessive
Phosphorylation by CDKs inactivate the RB protein, therefore ____.
allowing the cell to proceed from G1 to S
oncogenes
stimulate cellular proliferation
The RB protein is hyperphosphorylated in _____ at S or G2 of the cell cycle.
rapidly proliferating cells
LOH
loss of heterozygosity
FAP
familial adenomatous polyposis
Aneuploidy correlates with ________.
a poor prognosis
E6 protein inhibits _____.
p53
Cancer is not inherited as _______.
a single, Mendelian disease
