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CANCER General • A general grouping of all diseases related to unregulated cell growth • Cancers generally develop by an accumulation of mutations of the DNA • Begin at the DNA level Multi-hit hypothesis • All cancers appear to be the result of multiple DNA damage events • Each event causes that cell, and its descendents, to lose more and more control over the cell cycle • Eventually, a tumor may form • Then, if the cancer begins to leave, survive, and populate other regions of the body, we have metastasis - the growth of the tumor in other regions - this is cancer! DNA damage • Number of forms can lead to cancer 1. Direct changes to the DNA 1. Point mutations 2. Insertions and Deletions 2. Relocation of DNA 1. Translocation of chromosomes 2. Loss of chromosomes 3. Duplication of chromosomes 3. Viral and Transposon agents 1. Viruses can insert into critical genes 2. So may transposones Two mechanisms of action - 1) disruption of function, as shown here, or 2) disruption of homeostasis - bone cancer and Ca2+ 21_42_metastasis.jpg 21_43_Cancer_chromos.jpg 21_44_Tumors.jpg Common feature of cancer cells • • • • • • Reduced dependence of extracellular signals Less likely to undergo apoptosis Unregulated cell division Unstable - high mutation rate Invasive - they lack cell-adhesion molecules Survive in foreign tissues 21_45_proto_oncogenes.jpg 21_46_oncogene.jpg 21_47_cancer_pathways.jpg 21_48_Colorectal_cancer.jpg 21_49_APC_gene_mutat.jpg 21_50_APC_Wnt.jpg 21_51_tumor_cells.jpg 21_52_Gleevec.jpg QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.