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Unformatted text preview: Lecture 18- Cancer Four most common types of cancer in Canada-Breast cancer-Prostate cancer-Lung cancer-Colon cancer-40% of women, 45% of men can expect to contract some kind of cancer in their lives -Just less than 25% of women can expect to die from cancer, more than 25% of men can expect to die from cancer Likely factors contributing to cancer incidence in Canada-older you are, the more likely you are at developing cancer-Second most likely non-accidental cause of death (heart disease is the first)-Risk factors: exposure to dietary risk factors, exposure to environment-Lung and colon cancer suggest environmental risk factors-Breast and prostate cancer suggest internal risk factors-Balance of and interactions or internal and external factors that contribute to cancer Role of cyclin/CDK complexes in cell cycle regulation-Embryogenesis is rapidly diving cells-Cells may actively cycle, sit in G0 or undergo apoptosis-In the cell cycle there is a G1/s checkpoint that prevents cells from replicating their DNA if it is damaged-This is monitored by CDK (Cyclin Dependent Kinase) -CDK is a protein-It works by phosphorylating but only when it is bound to cyclin -CDK/Cyclin phosphorylates it target proteins together to release the G1/s checkpoint and cells proceed into S phase-This is an example of post-translational regulation-Constitutive expression- a gene that is transcribed continually compared to a facultative gene, which is only transcribed as needed-Production of cyclin is cyclic-Another CDK/cyclin complex regulates movement from S phase into M phase Uncontrolled Growth (1 st reason): Role of proto-oncogenes and oncomirs in caner-Proto-Oncogenes are essential for normal growth and development -EGFR (Epidermal Growth Factor Receptor)-It is a typical transmembrane protein -Active site outside the cell that binds protein hormone EGF-EGF stimulates the cell to divide -EGFR signals on the outside of the cell phosphorylation cascade signals presence of EGF on the outside of the cell causes the expression or no expression of certain genes in the nucleus-Any step along the pathway could be expressed inappropriately, causing it to become cancerous-When deregulated proto-oncogenes become cancerous and people call them oncogenes-Mutation is EGFR, causing it to signal even when EGF is not present, will lead to the cell dividing all the time up-regulation-How might proto-oncogenes be activated? Translocation issues, mutation in promoter (causes the promoter to be more attractive to polymerase, resulting in more expression), regulation problem with enhancers or repressors (enhancers become more effective than usual) Uncontrolled Growth (2 nd reason): Tumor suppressor genes and role of p53 gene-Suppressor gene work against proto-oncogenes to ensure that cell division occurs at a regular pace (genes that evolved to shut down rapid cell division)-TP53 is a master tumor suppressor gene; it codes a transcription factor that binds to the promoters of many target genes...
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- Fall '12