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4.1 Cancer: A Failure of Control over Cell Division 4.2 Common signaling molecules 4.3 Cell Cycle Regulation
The relative percentages of new cancers in the United States that occur at different sites
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Multiple cancer phenotypes arise from mutations in genes that regulate cell growth and division
Environmental chemicals increase mutation rates and increase chances of cancer Cancer has a different inheritance pattern than other genetic disorders Inherited mutations can predispose to cancer, but the mutations causing cancer occur in somatic cells Mutations accumulate in clonal descendants of a single cell
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Hormones transmit signals into cells through receptors that span the cellular membrane
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Signal transduction activation or inhibition of intracellular targets after binding of growth factor to its receptor
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Autocrine stimulation: Cancer cells can make their own stimulatory signals
a.1
Loss of contact inhibition: Growth of cancer cells doesn't stop when the cells contact each other
a.2
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Loss of cell death: Cancer cells are more resistant to programmed cell death (apoptosis)
a.3
Loss of gap junctions: Cancer cells lose channels for communicating with adjacent cells
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Cancer cells often have chromosome rearrangements (translocations, deletions, aneuploidy, etc)
Some rearrangements appear regularly in specific tumor types
Fig. 17.4b.2
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Phenotypic changes that enable a tumor to disrupt local tissue and invade distant tissues
Ability to metastasize: Tumor cells can invade the surrounding tissue and travel through the bloodstream
d.1
Angiogenesis: Tumor cells can secrete substances that promote growth of blood vessels
d.2
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Fig. 17.5a
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Tumor DNA
Transform normal mouse cells in culture with human tumor DNA
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Cancer can be caused by mutations that improperly inactivate tumor suppressor genes
Function of normal allele of tumor suppressor genes is to control cell proliferation Mutant tumor suppressor alleles act recessively and cause increased cell proliferation Tumor suppressor genes identified through genetic analysis of families with inherited predisposition to cancer Inheritance of a mutant tumor suppressor allele One normal allele sufficient for normal cell proliferation in heterozygotes Wild-type allele in somatic cells of heterozygote can be lost or mutated abnormal cell proliferation
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Mutant alleles of these tumor-suppressor genes decrease the accuracy of cell reproduction
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CDKs interact with cyclins and control the cell cycle by phosphorylating other proteins
Cyclin-dependent kinases (CDKs) family of kinases that regulate the transition from G1 to S and from G2 to M Cyclin specifies the protein targets for CDK Phosphorylation by CDKs can activate or inactive a protein
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CDKs mediate the transition from the G1 to the S phase of the cell cycle
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Disruption of the G1-to-S checkpoint in p53-deficient cells can lead to amplified DNA
Tumor cells often have homogenously staining regions (HSRs) or small, extrachromosomal pieces of DNA (double minutes)
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Disruption of the G1-to-S checkpoint in p53-deficient cells can lead to many types of chromosome rearrangements
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Cells with defective checkpoints are viable and divide at normal rates
But, they are much more vulnerable to DNA damage than normal cells Checkpoints help prevent transmission of three kinds of genomic instability Chromosome aberrations Changes in ploidy Aneuploidy
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