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33 Cards in this Set
- Front
- Back
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what are the characteristics of a cancer cell?
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-cancer cells do not respond to normal proliferation controls
-they may invade other tissues -may relocte to new sites -fail to self-destruct when abnormal -may promote blood vessel formation (angiogenesis) |
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How do cancer cells differ from normal cells ?
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-variation in cell size and shape
-enlarged nuclei -chromosomes look differentt -lots of nuclei -atypical mitosis |
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what are the most common cancers?
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1)SKIN CANCER
-prostate cancer -breast cancer -lung cancer -colon cancer |
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How are malignant and benign cancers distinguished?
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Benign: do not invade other tissue borders-> grow and expand but do not infiltrate
-do not metastisize -differentiated (resemble tissue of origin Malignant:metastasis to distant site, invades other tissues |
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What kinds of molecular defects cause cancer? (2)
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-mutations that activate oncogenes which stimulate cell growth
-mutations in tumor supressers that become inactivated which normally regulate cell growth |
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What are the most important components of cancer-related signal transduction pathways
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1)growth factor binds to receptor
2)receptors relay signal to cytoplasmic proteins by phosphorylation 3)cytoplasmic proteins: Ras is activated by receptor tyrosine kinases when it binds GTP 4)Ras transmits the signal to MAP which carries signal from cytoplasm to nucleus 5)MAP phosphorylates transc. factorps that activate transcription of target genes whose gene products promote cell cycle progretion |
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how does Ras get activated/ deactivated?
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-Ras is activated by GNRPs which stimulate release of GDP and bind GTP
-deactivated by GAPs which stimulate hydrolysis of GTP bound |
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what are the most important components of cancer-related cell cycle regulation?
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-CDKs which phosphorylate cyclins
-cyclins degrade in each division cycle in response to signal transduction -mitotic cyclins bind Cdk during G2(required for mitosis) -G1 cyclins bind Cdk during G1 (required for s phase) |
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How are these genes altered in cancer cells? (3)
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-w/ cancer there can be an overproduction of cyclin
-tumor suppressor genes are inactivated by a recessive mutation in 1 allele and the loss of the remaining wild type allele->loss of heterozygosity -P53 can be altered so that it cannot bind to the promoter-changes binding site and prevents the damage response and allowing cell proliferation |
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What are oncogenes and tumor suppressors and how are they relevant to cancer?
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oncogenes:activator and controller of cell growth, ex. Ras
tumor supressor: deactivated in cancer cell, normally stop growth ex. P53: checkpoint transc. factor, turns on genes involved in apoptosis, an inhibitor of cell cycle progression by inducing p21 which inactivates cdk required for DNA synth. Rb: controls transc. of genes needed for cell cycle by stopping transc. factors by binding to E2F transc. factor -CDK can phosph. Rb (inactivating it)which allows the transc. factors to have access to binding sites |
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What is the mutagenesis model for cancer production
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-initial mutation cretes a mutator precuror cell which then produces muatations at high levels
mutator cells have defects in: cell cycle regulation dna replication fidelity dna repair |
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p53 is activated when?
what does it bind to? what is its funtion? |
activated following DNA damage
binds to promoter funcions to promote transc. of genes involved in the damage response ex. inhibits g1/ s transition by induces p21 (reduces cdk required for dna synth) -also inhibits g2/m transition by lowering intracell conc. of cyclin required for mitosis - |
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How does Rb dissasoc. from E2f which is bound to promoter?
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it gets phosphorylated by cyclin/cdk complex which allows E2F to activate transc. which promotes progress to s phase
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how does p21 relate to Rb ?
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p21 is up-regulated by damage and p53 activation
-it inhibits cdks so Rb remains in active (non phosphorylated form)-growth inhib. state |
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What celluar systems are defective in early stages of cancer?
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coding and regulatory regions of the genes-> mutations lead to alternate proteins or abnormal expression
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what types of mutations cause cancer?
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-sing base change (point mutation)--may change indiv. aa's or prematurely truncate encoded protein
-insertions/deletions: change reading frame leading to altered protein seq. or truncation -Genome rearrangements: (translocations) especially in leukemias -may cause gene activation: gene is moves to new location where its expression is altered by near-by regulatory sequences or may cause gene fusion: piece of gene inserted in another gene sequence so coding seq. is on same reading frame for both genes. Hybrid gene is formed and may be expressed at altered levelsor translation product may have unusual functional properties -more gene fusion:usually in blood diseases, transcription factor is usually involved causing inapprop. gene expression |
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How do these mutations affect oncogens and tumor suppressors differently?
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oncogenes:in tumors they are activated by mutations which either overproduce protein or allow expression under inaprop. conditions--result in gain of function
tumor suppressors:become inactivated and fail to suppress growth |
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What steps during DNA replication prevent cancer/
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Replicaton errors are from failure of DNA pol to incorp. correct nucleotides
minimize mutations by: -correct insertion of nucleotides by dna pol -proofreading by exonuclease -use of specialized polymerases to replicate past DNA damage (by-pass polymerases) -post-replication repair process (mismatch repair) |
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what disease has abnormal by-pass polymerase? and what is the polymerase it's supposed to have ?
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XPV: defects in DNA pol n
-prevents accurate by-pass of uv damage and lets a less acc. polym form the bypass resulting in excess mutation |
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What is mismatch repair and how is it related to cancer?
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mismatches are recognized by MutS.
-MutS makes a complex with MutL and Mut H allowing Mut H to nick the DNA -nucleases remove a strech of DNA including mismatch -resulting gap is filled by dna pol and sealed by ligase |
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how does the mismatch system know wich strand to repair?
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MutH identifies the unmethylated A and cuts it out
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why do we have mismatch repair in colon cancer?
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colon tissues are rapidly growing and replicating
-blood cancer also shows mismatch |
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Colorectal cancer has mutations where?
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mismatch repair defects in MutS o MutL
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What is nucleotide excision repair and how is it related to cancer?
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1)damage recognition by XPA and XPC
2)incision 3)damage removal 4)gap filling DNA synthesis 5)ligation |
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what diseases are caused by defects i n this mechanism?
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XP:exhibit defects in recognition or incision steps not dna pol or ligase
-TTD and Cockayne syndrom mutations are found in CSA and CSB |
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when is XPC needed?
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when you don't have transcription, so in general repair and recognition--so mutation is in XP not CS
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what are XPD and XPB
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they are inside TFIIH and act to target nucletotide excision repair and are needed for promoter recognition by RNA Pol
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What is homologous recombination and how is it related to cancer?
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homologous recombination repairs breaks in dna
1)dna ends in a break and transformed to ssDNA 2)RAD51 protein is targeted to ssDNA and promotes pairing to homologous duplex -repairs double strand breaks |
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How is homologous recomb related to cancer?
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Indiv. with muations in BRCA1 and BRCA 2 develope breast cancer
-normal BRCA allele is lost so tumor is homozygous |
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what happens in absence of BRCA2?
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RAD51 promoted homologous recomb is impaird
-in BRCA2 breast cancer cells complex formation between RAD51 and BRCA2 is disrupted and RAD51 remains in cytoplasm |
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what sorts of genetic diseases make us cancer prone?
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XPV-missing bypass polymerase
XP-missing nucleotide excision repair breast cancer-missing BRCA2 and Rad51 can't function colorectal cancer-mismatch repair deffects in MutS or MutL Li-Raumeni syndrome -p53 |
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what is UVB?
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sunburn, results in damage to epidermal cells
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UVA?
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penetrated deeper than UVB
phot-aging rather than sunburn |
