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Lecture 19

Biology 1002B Lecture 19: Class 19 – Regulation and Cancer

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Biology 1002B
Denis Maxwell

Class 19 Regulation and Cancer Most common cancers in Canada Prostate, breast, colon, lung Prostate and breast are sexspecific not explained by genetics Colon and lung are due to environmental mutagens Reasons why identical twins may have different cancer incidence Due to different methylation patterns Different methylation = different genes being expressed Methylation patterns can be subject to genetic change and environmental change Reasons why cancer mortality varies across geographical areas in Canada Environmental causes, social causes, diet, ethnicity, access to health care and treatment, etc.. Relatively low in BC, relatively high in Nunavut How DNA methylation can regulate gene expression Directly: affect binding of transcription factors (i.e. to tumour suppressor genes; downregulates them which causes cell proliferation or to genes coding for miRNA that binds to protooncogenes, which causes them to go crazy fast and stimulate lots of cell division) Indirectly: attract HDACs (histone deacetylases), which deacyetylate the histones causing them to hold on to the DNA tighter and makes them less accessible for transcription Basic characteristics of cancer cells Divide like crazy Evade growth suppressors Activate invasionmetastasis; resist cell death, etc. Relative heritability of cancer in humans Low (0.270.41); not very likely for twin to get it Role of protooncogenes, tumor suppressor genes and oncomirs in normal organismal metabolismdevelopment. Protooncogenes Protooncogenes are in normal cells; stimulate cell division In cancer cells, protooncogenes are deregulated to oncogenes, which stimulate cell division to cancerous state Note that only one of the two protooncogene alleles need to be altered for changes (wild type is recessive) Ways to convert protooncogene to oncogene: Mutation in genes promoter or other control sequences; becomes abnormally active Mutation in the coding segment of gene; altered form of encoded protein Translocation (DSB in chromosome); moves gene to more powerful promoter Infecting viruses can introduce genes; disrupt cell cycle or alter regulatory proteins to turn genes on in the host Tumor Suppressor Genes Encode proteins that inhibit cell division; best known one is TP53 (p53 protein)
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