Neoplasia 2 Flashcards by Chris Rodarte

expression mutated gene, abnormal expression quiescent gene, gene amplification, loss growth inhibitory genes

expression mutated gene, abnormal expression, quiescent gene, gene amplification, loss growth inhibitory genes

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nuclear regulatory proteins

myc, myb, jun, fox

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nuclear regulatory protein in Burkitt’s lymphoma

c-myc

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nuclear regulatory protein in neuroblastoma

N-myc

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tumor supressor genes -> must have loss of BOTH copies

RB, p53, NF-1, DCC (deleted in colon cancer)

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cancers with high correlation of ras mutation

colon, pancreas, thyroid (glandular)

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single most common abnormality of dominant oncogenes in human tumors

ras

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two hit hypothesis of retinoblastoma (40% familial cases, malignant retinal tumor)

one mutated from parent, other does somatic mutation

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single most common target for genetic alterations in human cancer (RECESSIVE also)

p53

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this oncogene acts as “policeman” to inhibit division of genetically damaged cells to allow for repair (quiescence, senescence, or apoptosis) -> typically UV light damage and carcinogenesis

p53

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p53 can cause this: temporal cell cycle arrest that allows for repair

quiescence

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p53 can cause this: induction of permanent cell cycle arrest (if repair doesn’t happen)

senescence

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what mediates cell cycle arrest in p53 action?

CDK inhibitor p21

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what mediates apoptosis from p53 activation?

BAX

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these tumors are more susceptible to chemotherapy and radiation

normal p53

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what is a complete carcinogen?

carcinogen that induces initiation and promotion

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what can carcinogens (reactive electrophiles) attack?

DNA, RNA, proteins

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chemical carcinogen associated with angiosarcoma of the liver

vinyl chloride (PVC)

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fungus that infects peanuts -> has aflatoxin B1

aspergillus flavus

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Aspergillus flavus is associated with this cancer

hepatocellular carcinoma

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malignant forms of HPV have these proteins that cause cancer; what do they inactivate?

E6 and E7; p53, Rb (respectively)

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ways you can look for clonality (expression of specific alleles in daughter cells)

methylation patterns, indicators identical gene RAR (like Ig and T cell isotype)

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primary target for genetic damage in neoplasm formation

growth regulatory elements

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4 classes of normal regulatory proteins that are targets for alteration causing autonomous proliferation

growth promoting oncogenes, growth inhibiting tumor suppressor genes, genes regulating apoptosis, genes regulating DNA repair

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non-altered gene present in normal cells that can then become altered or expressed

proto-oncogene

oncogenes that promote growth are these kind -> only need one allele mutated; what are some examples?

dominant; RAS, GF, GFR

oncogenes that inhibit growth are these kind -> BOTH alleles must be mutated; what are some examples?

recessive; p53, Rb

what is necessary for total unregulated growth to occur in oncogenesis?

constitutive expression multiple positive growth signals and loss inhibitory signals

when does the first restriction point occur in cell cycle?

after G1

regulates orderly progression through the cell cycle phases

cyclins and CDKs

these phosphorylate critical regulatory proteins in the cell cycle

CDKs

this activates CDK, which then activates Rb; what phase is it present in?

cyclin D; mid G1 (disappears in S due to ubiquitin-proteasome)

EF2 transcription

E2F transcription

this cyclin/CDK permits DNA replication (through the S phase)

cyclin E/CDK2

this regulates mitotic prophase

cyclin A/CDK2

this regulates nuclear division

cyclin B/CDK1

class of CDK inhibitors -> p21 is part of it (which is activated by p53)

CIP/WAF

two check-points to prevent duplication of damaged cells

G1/S, G2/M

what does G1/S checkpoint act through?

p53

four key regulators of cell cycle -> dysregulated in majority of human cancers

p16/INK4a, cyclin D, CDK4, Rb

this inhibits transcription of proteins required for S phase -> prevents entry into G1

growth inhibition of damaged cells and apoptosis

p53

how does a cell differentiate?

going through successive cell divisions

Xeroderma pigmentosum is caused by this

loss of nucleotide excision repair pathway, can't excise pyrimidine dimers (DNA repair)

mechanisms by which oncogene can be activated

change in structure (point mutation) or regulating element (translocation, other oncogene), gene amplification, viral transformation, epigenetic methylation

mutation in this can cause increased gene expression of growth factors -> forming oncogene

RAS

how can GFRs become oncogene?

constitutive activation, overexpression (gene amplification, translocation)

how can signal-transducing proteins be oncogenes?

constitutive activation ras/g proteins or activation regulatory kinases

this protein prevents programmed cell death -> overexpression allows damaged cells to survive and mutations to be expressed

bcl-2

this acts as break to prevents cell from moving from G0 to G1

does phosphorylation activate or inhibit Rb?

inactivates (inhibits the inhibitor...dissociates from EF2 and allows replication)

protein/oncogene involved in malignant melanoma

p16(INK4a)

this phosphorylates Rb (inactivating it)

cyclin D/CDK4

does loss of p53 usually occur late or early in stepwise progression of DNA changes?

late (allows for duplication of DNA-damaged cells)

this syndrome is related to inheritance of mutated allele of p53 (similar to two-hit hypothesis) -> greatly increases chance of developing malignant tumor by age 50

Le Fraumeni syndrome

this virus (among others) can inhibit p53 function

papilloma

Bcl overexpression (associated with translocation) is seen in this condition

B cell lymphoma

potential oncogenes that induce pores in mitochondrial membrane to release cytochrome C

BAX, BAK

defective mismatch repair resulting in microsatellite instability

Hereditary non-polyposis cancer syndrome

these diseases are associated with improper activation of p53 due to strand breaks

ataxia-telangiectasia, Bloom syndrome, Fanconi anemia

BRCA1, BRCA2 normally have this role in DNA repair

repair DNA breaks

this enzyme is upregulated in 85-95% of cancers

telomerase (active normally only in germ cell and stem cells)

examples of promoters of transformation

hormones, cytokines, GF (any mitogenic stimulus)

induction of oncogenic DNA changes by environmental agent -> most cause initiation

carcinogenesis

mechanisms of gene alteration in carcinogenesis

mutagenesis, translocation, gene amplification, insertion transcription element (viral)

what metabolizes most carcinogens

p-450 dependent mono-oxygenase

vast majority of initiating chemicals are these

mutagens

primary target of carcinogens

DNA

these chemical carcinogens require metabolic activation -> tobacco smoke, broiling animal fats, smoked meat/fish

polycyclic aromatic hydrocarbons

these chemical carcinogens have been associated with bladder cancer

B-naphthylamine, aniline dyes

chemical promoters (carcinogens)

phorbol esters, saccharin and cycylamates, estrogens, dietary fat

ionizing radiation types

electromagnetic, particle

mechanism of action for xray/gamma ray radiation

indirect (free radical)

MOA for radiant energy radiation damage

indirect and direct

MOA for particulate radiation damage

direct

these are formed due to radiation damage of DNA

pyrimidine dimers and crosslinks, single and double strand breaks, RAR

UV light affects these layers/can cause these cancers; what forms as a result of UV damage?

squamous cell, basal cell, melanoma; pyrimidine dimers

what bands of UV light radiation are most dangerous/harmful?

middle B bands

ca associated with miners of radioactive elements

lung cancer

ca associated with atomic bomb survivors (ionizing radiation)

leukemia

ca associated with therapeutic exposures (ionizing radiation)

thyroid

ca associated with radium dial painters

mouth, throat (because licked paint brush)

this radiation often causes leukemia (except chronic lymphocytic)

ionizing

cells are sensitive to radiation directly proportional to this level, inversely to this

reproductive/mitotic activity, level of specialization

what is HPV oncogene associated with -> stable integration of viral DNA into host DNA

squamous cell ca cervix

integration of malignant HPV subtypes involves alterations in these proteins

Rb and p53

malignant cancers associated with EBV infection

Burkitt's lymphoma, B cell lymphomas (immunosuppressed), Hodgkin's disease, nasopharyngeal carcinoma

what cells are infected by EBV?

epithelial and B cells

what occurs due to HBV oncogene -> chronic liver cell injury with regenerative hyperplasia

expression HBx protein, increase protein kinase C

this virus causes cancer from chronic inflammation (*not direct oncogene/insertion*)

HCV

human herpes type 8 is associated with this cancer

Kaposi's sarcoma

this has tropism for CD4, transmission is same as HIV -> see T cell proliferation plus 2nd mutagenic event (*latent 20-30 years*)

human T cell leukemia/lymphoma

Neoplasia 2 Flashcards

(92 cards)