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34 Cards in this Set
- Front
- Back
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metastasis
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move to distant places in the body...traceable to original site or primary tumor
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benign
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tumors growing locally without invading adjacent tissues
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malignant
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tumors invading nearby
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most tumors arise from?
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epithelial cells
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mesothelioma
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asbestos exposure and cigarette smoking
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exposure to benzopyrene may lead to what tumors in mice?
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skin
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What % does cancer account for?
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20%
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loss of cellular regulation due to:
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self-sufficiency of growth signals
insensitivity to antigrowth signals evasion of apoptosis limitless replicative potential sustained angiogenesis tissue invasion and metastasis |
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mutations in what two important classes of genes are involved in cancer?
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proto-oncogenes
tumor suppressor genes |
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tumor suppressors are:
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apoptotic proteins
cell-cycle control proteins dna-repair proteins |
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growth promoting proteins are:
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signaling molecule
signal receptor intracellular transducers intracellular receptors transcription factors |
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phosphorylated residues on proteins provide docking sites:
phosphorylated proteins bind to: |
enzymes such as phospholipace C-gamma or orhter tyrosine kinases to relay signal
adaptor proteins and connect receptors to downstream signaling proteins such as RAS |
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What is RAS?
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monomeric GTPase
an oncogen that is activated in 30% of human tumors |
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Ras can be activated either by activating ___ or inhibiting _____
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act-GEF
inh-GAP |
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activated RTK allows ____ binding, which binds Ras GEF.
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Grb-2 adaptor binding
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What happens after the activation of Ras?
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a cascade of phosphorylatino rxns occur to relay the signal to the nucleus
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What's the end result of the signal carried by Ras?
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cell proliferation genes such as G1 cyclins are turned ON
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The core kinases of Ras include these three serine/threonine kinases:
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MAPKKK (Raf Kinase)
MAPKK (Mek Kinase) MAPK (Erk Kinase) |
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ErbB
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Her2/neu is amplified in breast cancers
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How are Cdks regulated?
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cyclin dependent kinases are regulated by cyclins D, E, A, B...which are synthesized and degraded in each cycle.
CAK, CKI (cdk inhibitor proteins) phosphatases |
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unreplicated DNA blocks what?
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it's a negative signal to block M-Cdk activation (inactive phosphorylated Cdk)
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What is M-Cdk involved in?
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mitotic spindle assembly
chromosome condensation nuclear membrane breakdown actin rearrangement sister chromatid separation (mediated by anaphase promoting complex: ubiquitin ligase?) |
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D cyclins 1, 2, 3 bind to what?
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CDK4 or CDK6
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E1 and E2 bind
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CDK2
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A1 and A2 bind to what
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CDK2 or CDC2
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B1 and B2 bind?
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CDC2
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Rb
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retinoblastoma is a tumor of retina.
familial: tumor in both eyes sporadic: tumor in only one eye |
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Knudson conclusions
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1. rate of familial tumor appearance consistent with a single random genetic hit
2. rate of sporadic tumor appearance consistent with two random genetic hits |
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Rb locus on chromosome 13q14 also encodes for what enzyme?
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esterase D, which has 2 isoforms or allels that migrate differentially on electrophoresis gels
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what is the function of Rb?
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G1 progression inhibition
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for s-phase initation, cell transcribe specific genes mediated by what?
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transcription factor E2F
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E2F activity is regulated by what?
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retinoblastoma protein, which is an inhibitor of cell cycle progression
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what is GAP?
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GTPase activating protein
Ras activated by inhibiting GAP |
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What is GEF?
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guanine nucleotide exchanger factor
Ras activated by activating GEF |
