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Lecture 26 Cancer - IPHY 3060 Lecture 28 Cancer Cancer...

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IPHY 3060 Lecture 28: Cancer
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Cancer
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Cancer Cancer is a disease characterized by excessive, unregulated, and disruptive proliferation of cells that interferes with normal tissue function
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Key Point: Cancer starts when changes occur to genes regulating cell proliferation
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3 sources of DNA changes Differences in the DNA sequence inherited from our parents Errors in DNA copying during DNA replication Changes that accumulate over the lifespan of an organism as a result of exposure to DNA damaging agents
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Inherited Changes Variations in the DNA sequence inherited from our parents These variations usually slightly change the amount or activity of the resulting protein Ordinarily these changes aren’t enough to cause cancer unless we inherit two bad copies of a gene critical for regulating cell proliferation However, they can predispose us to certain kinds of cancer by increasing the likelihood of cells becoming over- proliferative
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DNA Copying Errors Occasionally the DNA synthesis machinery mistakenly adds the wrong base to a DNA sequence Ordinarily small mistakes made in copying DNA are detected and corrected by DNA “proofreading” and repair enzymes Mutations to these enzymes can make them less effective at finding and correcting mistakes
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DNA damaging agents Radiation Chemical carcinogens Reactive oxygen species
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Cancer mutations induce one of two changes: Change the quantity of a protein Change the activity of a protein
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Change the quantity of a protein 1) Transcription —change to promoter region sequence 2) mRNA stability —change to 3’ UTR sequence 3) Protein stability —change to protein sequence resulting in a change in degradation
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Change the activity of a protein 1) Change in activation of a protein— constitutively active 2) Change in specificity of a protein Kinase X Protein Y P Kinase X P Protein Z Kinase X Active Kinase X Inactive P Kinase X Mutation to unphosphorylatable amino acid; kinase X can no longer be inactivated by phosphorylation
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3 Types of Genetic Changes Point mutation —single base change Translocation —bring parts of two different genes together Amplification/deletion -- abnormal DNA replication so that multiple copies of a gene are made, resulting in over-production, or abnormal deletion of DNA sequences Myc Myc Myc
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Point Mutation Can change protein quantity by altering transcription factor binding site, RNA stability, protein stability, etc. Can change protein activity by altering phosphorylation/ activation, specificity, etc.
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Translocations Can change protein quantity by bringing the coding region of one protein under control of a more active promoter Can change protein activity creating a fusion protein with properties of both
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