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 originateo Can vary in their ages of onset, growth rates, invasiveness, prognoses, and responsiveness totreatmentso At the molecular level, all cancer exhibit common characteristic that unite themo All share two fundamental properties that are caused by genes that were either mutated or 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 bodyo 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 harmo 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 bodyo 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 mutationo 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 intoa mature cell type and one that remains a stem cello Cancer involves the accumulation of multiple mutationso 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 mistakeso Carcinogens: cancer causing agents, exposure to radiation of the atomic bomb- Genomic instability is a hallmark of cancero Genomic instability: The presence of gross defects such as translocation, aneuploidy, chromosome loss, DNA amplification, and chromosome deletionso 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 problemo Double minute chromosomes: extra pieces of DNA existing outside chromosomes, just floatingaroundo 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 normalo XP mutation: lacks ability to repair thymine dimer from UV lighto 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 cancero Cell regulation falls aparto 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 G0o Checkpoints are screwed up as wello 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 processeso 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 impossibleo 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 cycleo When messed up it becomes an oncogeneo 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 theprocess of apoptosiso When mutated or inactivated, cells are unable to respondo 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 cancerso 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 bladdero Retinoblastoma: in inherited disorder in which tumors develop in the eyes of young children Loss of heterozygosityo 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 bodyo 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 streamo Type of cancer that ends up killing peopleo Cells break free and the tumor suppressor has to express enzymes to let them leaveo They also show things that help them go through tissueso They have target organs - Most cancers are sporadic, 1-2% can have heredity o familial componento 1% Colon cancer- familial adenomatous polyposis (FAP) Individuals inherit one mutant copy of the APC geneChapter 19: Cancer and Regulation of the Cell Cycle Summary (Page 3)o Cancers can vanish on their own Epigenetic: change in chromosome structureo Viruses contribute to cancer- Environmental agents contribute to human cancers:o Sun, smoking,