Chapter 19 Cancer and Regulation of the Cell Cycle Summary Page 1 Cancer is a large number of complex diseases up to a hundred that behave differently depending on the cell types from which they originate o Can vary in their ages of onset growth rates invasiveness prognoses and responsiveness to o At the molecular level all cancer exhibit common characteristic that unite them o All share two fundamental properties that are caused by genes that were either mutated or treatments expressed inappropriately Proliferation abnormal cell growth and division Metastasis defects in the normal restrains that keep cells form spreading and colonizing other parts of the body o Benign Tumor when a cell loses control and proliferation occurs the cells may grow into a multicellular mass which can be removed by surgery and may cause no serious harm o Malignant tumors often difficult to treat and may before life threatening because of its metastasis where the cells begin to travel in the blood stream and spread throughout the body o Male getting cancer 50 female 33 prostate very uncommon Colonial Origin of Cancer cells a certain cell obtained a mutation and multiplies not all the cells in cancer are identical heterogenetity o Tumors can recruit cells to form more mutation o Cancer Stem Cell Hypothesis tumors are comprised of a mixture of different cells many don t proliferate but the ones that do crease cancer stem cells Stem cells are cells that have the capacity for self renewal a process in which the stem cell divides unevenly creating one daughter cell that goes onto differentiate into a mature cell type and one that remains a stem cell o Cancer involves the accumulation of multiple mutations o Probability of cancer increase with age because Cells accumulated several mutations to become cancerous As you get older DNA repair decreases so cant fix as many mistakes o Carcinogens cancer causing agents exposure to radiation of the atomic bomb Genomic instability is a hallmark of cancer o Genomic instability The presence of gross defects such as translocation aneuploidy chromosome loss DNA amplification and chromosome deletions o Defective DNA repair cells cannot repair damage leading to cancer Epigenetics is the study of factors that affect gene expression but that do not alter the nucleotide sequence of DNA Gene amplification process where one or more genes copy at too high of a level creating a problem o Double minute chromosomes extra pieces of DNA existing outside chromosomes just floating around o Homogeneous staining region uses fluorescence probe to show a particular gene if stain and region of chromosome is stained all the same then if there is only two spots then it is normal but if there are a lot of stained spots than it is not normal o XP mutation lacks ability to repair thymine dimer from UV light o Brca1 and Brca2 involved in DNA repair defect typically leads to breast cancer Translocations Philadelphia chromosome BCR and ABL combine and form chronic myelgenous leukemia CML o Has a drug targeting BCR able protein which is an effective treatment Provenge prostate cancer HNPCC mutations in mismatch repair born with this problem then the probability of cancer is high lynch syndrome as well Chapter 19 Cancer and Regulation of the Cell Cycle Summary Page 2 o Chromosomal instability is more common mismatch repair typically has messed up microsatellite repair Cell growth in cancer o Cell regulation falls apart o Most cells are supposed to stay in G0 phase where they don t move through the cell cycle but in cancer cells they skip over G0 o Checkpoints are screwed up as well o Cyclin helps control progress through the cell cycle the cell will delete cyclin in a precise manner during the cycle they come on off throughout the cell cycle to regulate processes o Cyclin dependent kinases enzyme that phosphorylates proteins Control of apoptosis programmed cell death occurs when DNA or a chromosome is damaged so severely the repair is impossible o Defects that occur in cancer of apoptosis Cancer inhibits apoptosis continuing to grow and divide instead of killing itself Bcl2 and BAX proteins an trigger or prevent apoptosis Bcl2 is over expressed in cancer preventing apoptosis Proto oncogenes encode transcription factors that stimulate expression of other genes signal transduction molecules that stimulate cell division and cell cycle regulators that move the cell through the cell cycle o When messed up it becomes an oncogene o Ras Proto oncogenes ras protein is involved in signal transduction turning on transcription factor In cancer its stuck on always active Tumor suppressor genes genes whose products normally regulate cell cycle checkpoints or initiate the process of apoptosis o When mutated or inactivated cells are unable to respond o If heterozygous good chance eventually you ll lose dominate allele P53 guardian of the genome tumor suppressor gene is mutated in more than 60 of cancers o Induced by DNA damage protein induced by post transitutional No stress degradation Stress transcription activation and p53 accumulation RB1 tumor suppressor when mutated contributes to the development of many cancers including those of the breast bone lung and bladder o Retinoblastoma in inherited disorder in which tumors develop in the eyes of young children Loss of heterozygosity o When cell goes from G1 to S phase cylcin has pRB as a target Normal grabs transcription factor Messed up doesn t see it Metastasize cancer cells invade other tissues in the body o Extracellular matrix and basal lamina surround and separate body tissues Metastasize cancers dissociate from tumor and secrete proteases that digest these surrounding to break free to the blood stream o Type of cancer that ends up killing people o Cells break free and the tumor suppressor has to express enzymes to let them leave o They also show things that help them go through tissues o They have target organs Most cancers are sporadic 1 2 can have heredity o familial component o 1 Colon cancer familial adenomatous polyposis FAP Individuals inherit one mutant copy of the APC gene Chapter 19 Cancer and Regulation of the Cell Cycle Summary Page 3 o Cancers can vanish on their own Epigenetic change in chromosome structure o Viruses contribute to cancer Environmental agents contribute to human cancers o Sun smoking etc