molecular biology of cancer · different cancers tend to form metastases at particular secondary...
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Molecular View of Cancer
Lecture 3:
How do cancer cells move?
How do errors occur in cancer cells?
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How do cancer cells invade healthy tissue and metastasize?
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Cells “let go” and migrateCells must lose intercellular adhesion and acquire migratory ability
http://www.youtube.com/watch?v=rrMq8uA_6iA
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Different cancers tend to form metastases at particular secondary sites 1° tumor
(melanoma)
2° tumor in brain(melanoma)
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How do errors occur in cancer cells?
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Cancer Tends to Involve Multiple Mutations
Malignant cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
More mutations, more genetic instability, metastatic disease
Proto-oncogenes mutate to oncogenes
Mutations inactivate DNA repair genes
Cells proliferate
Mutation inactivates suppressor gene
Benign tumor cells grow only locally and cannot spread by invasion or metastasis
Time
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Multiple pathways to cancer
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Other factors influence tumorigenesis
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Viral infection and cancer
Virus Associated cancer(s)
Epstein-Barr virus (EBV, “mono”) Burkitt’s lymphoma, nasopharyngeal carcinoma
Hepatitis B and C Liver cancer
Herpes virus-8 Kaposi sarcoma
Human T lymphotrophic virus type 1 (HTLV-I)
T-cell leukemia
Human papilloma virus (HPV) Cervical, genital and oral cancers
Viruses can promote cancer via chronic inflammation or by preventing apoptosis
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Other factors influence tumorigenesis
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DNA is continually damaged
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DNA Repair Genes
Cancer
No cancer
No DNA repair
Normal DNA repair
Base pair mismatch
T CATC
A GTCG
T CAGC
A GTCG
A GTG A GTAG
T CATCT CATC
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Heritable cancer syndromes/predisposition
• A mutation in genes involved in DNA repair can lead to cancer syndromes
• DNA repair genes are tumor suppressors
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Heritable cancer syndromes/predisposition
• Xeroderma pigmentosum (XP)
• Hereditary breast cancer
• Hereditary non-polyposis colorectal cancer (HNPCC)
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Cancer cells show genome instability
• Chromosome rearrangements, changes in copy number, and mutations can both facilitate carcinogenesis and be a result of it
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p53 is one of the most important tumor suppressors we have
• Needed for successful DNA repair
• Can halt cell division• Can induce cell death if
cell too damaged
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p53 is one of the most important tumor suppressors we have
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p53 and cervical cancer
E7 blocks Rb!
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Li-Fraumeni Syndrome: a severe cancer syndrome
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Next time: Epigenetics and cancer, and cancer therapies