Upload
others
View
5
Download
0
Embed Size (px)
Citation preview
Molecular View of Cancer
Lecture 3:
How do cancer cells move?
How do errors occur in cancer cells?
How do cancer cells invade healthy tissue and metastasize?
Cells “let go” and migrateCells must lose intercellular adhesion and acquire migratory ability
http://www.youtube.com/watch?v=rrMq8uA_6iA
Different cancers tend to form metastases at particular secondary sites 1° tumor
(melanoma)
2° tumor in brain(melanoma)
How do errors occur in cancer cells?
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
Multiple pathways to cancer
Other factors influence tumorigenesis
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
Other factors influence tumorigenesis
DNA is continually damaged
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
Heritable cancer syndromes/predisposition
• A mutation in genes involved in DNA repair can lead to cancer syndromes
• DNA repair genes are tumor suppressors
Heritable cancer syndromes/predisposition
• Xeroderma pigmentosum (XP)
• Hereditary breast cancer
• Hereditary non-polyposis colorectal cancer (HNPCC)
Cancer cells show genome instability
• Chromosome rearrangements, changes in copy number, and mutations can both facilitate carcinogenesis and be a result of it
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
p53 is one of the most important tumor suppressors we have
p53 and cervical cancer
E7 blocks Rb!
Li-Fraumeni Syndrome: a severe cancer syndrome
Next time: Epigenetics and cancer, and cancer therapies