Exam 4 Chapter 16 Cancer is the leading cause of death in Western countries o 1 and 3 people will develop cancer o Cancer is a genetic disease at the somatic cell level therefore is it is characterized by the presence of gene products and derived from mutated or abnormal genes Cancer is a genetic disease that occurs through mutations derived in 16 1 somatic cells What is Cancer o It rises from an accumulation of mutations in many genes Mutations affect cellular functions repair of DNA damage cell division apoptosis cellular differentiate migration behavior and lastly cell cell contact o Cancer is clinically defined as a large number of complex diseases up to 100 that behave differently o Common characteristics found in cancer Abnormal cell growth and division Proliferation Defects in the normal restraints that keep cells from spreading and invading other parts of the body Metasis o Genes are mutated or are expressed inappropriately Therefore uncontrolled cell proliferation and metastatic spread will result in dangerous cancer cells o When a cell simply loses genetic control over cell growth it may grow into a multicellular mass or a Benign tumor Benign tumors can be fixed through surgery and are typically harmless o On the other hand if the cells in the tumor are able to break loose enter the bloodstream invade other tissues as well as form secondary tumors Metastases they become malignant Malignant tumors These tumors are difficult to treat and can be extremely o All cancer cells in primary and secondary tumors are clonal meaning they are derived from a common ancestral cell and because of their pattern of the X chromosome inactivation o Burkitt s lymphoma cancer cell showing reciprocal translocations between chromosome 8 and chromosomes 2 14 or 22 Translocation breakpoints at or near the c myc gene Breakpoints at or near one of the immunoglobin dangerous Origin of Cancer Cells The Cancer Stem Hypothesis genes o 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 on to differentiate into a mature cell type and the other remains a stem cell Cancer stem cells have been found in leukemias solid tumors in the brain breast colon ovary pancreas and prostate Cancer as a Multistep Process Requiring Multiple Mutations o A single mutation is not sufficient enough to develop cancer o In humans mutations occur at a rate of 10 6 mutations per gene per cell division due to error rates of DNA replication Therefore 1 person in 3 will suffer from cancer o Age related incidence of cancer suggest that many independent mutations occurs randomly o Another indication is Carcinogens cancer causing agents and the appearance of cancer o Cancer occurs in a series of steps For example each step in tumorigensis or the development of a malignant tumor result from 2 or more genetics alterations that release the cells progressively from the controls that normally operate on proliferation and malignancy It is believed that driver mutations may be what gives a growing advantage to a tumor cell 16 2 Cancer cells show a higher than normal rate of mutation chromosome abnormalities and genomic instability Many believe that the defect in cancer may result from the derangement of a cells normal ability to repair DNA damage Loss of genomic instability will result in the increase of mutation rates for every gene in the genome Mutator phenotype high level of genomic instability Genomic Instability and Defective DNA Repair o Genomic instability is expressed through defects in translocations aneuploidy chromosome loss DNA amplification and chromosome deletions Cancer cells grown in cultures have an increase in genomic instability o Chronic myelogenous leukemia CML white blood cells from patients bear a specific translocation in which the c ABL gene on chromosome 9 is translocated into the BCR gene on chromosome 22 This translocation creates a structure known as the Philadephia chromosome o The normal ABL proteins is protein kineases which acts within a signal transduction pathways transferring growth factor signals from the external environment to the nucleus o Cancer that caused by defects in genes that control DNA repair Xeroderma pigmentosum XP a rare hereditary disorder that is characterized by extreme sensitivity to UV light and other carcinogens Skin cancer cells are defective in nucleotide excision repair mutations in 1 of 7 genes whose products are needed to carry out DNA repair o Hereditary nonpolyposis colorectal cancer HNPCC caused by genes that go through mutations during DNA repair autosomal dominant syndrome syndrome 1 to every 200 to 100 people increase risk of developing colon ovary uterine and kindey cancer cells show a higher than normal mutation rates and genomic instability 8 genes are associated with HNPCC and 4 of these genes control aspects of DNA mismatch repair Inactivation of the following four genes will result in genomwide mutations and the subsequent development of colorectal and other cancer MSH2 MSH6 MLH1 and MLH3 Chromatin modification and cancer Epigenetics o Cancer cells contain major alteration in DNA methylation Much less methylation in cancer cells o Promoters of some genes are hypermethylated in cancer cells All of this may result in transcription repression for some genes therefore genes can t regulate normal cellular functions o Histone modifications are also disrupted in cancer cells o There may be more epigenetic defects than gene mutation in cancer cells 16 3 barely divide Most extreme example of nonproliferating cells are nerve cells which Multicelllular organisms are able to replace dead and damaged tissue due to differentiated tissues liver and kidneys when introduced to extracellular signals and growth factors Normal cell proliferation o Programmed cell cycle cell death and response to cells of growth signals The Cell Cycle and Signal Transduction o Cancer cells are unable to enter the G0 quiescent phase instead they keep cycling o Cells can be stimulated to renter the cell cycle even when they re in the G0 through external growth signals which are delivered through growth factors and hormones that bind to cell surface receptors o Signal transduction A process of transmitting growth signals from the external environment to the cells nucleus Overall it initiates a program of gene expression that stimulates the cell out of the G0 phase back into the cell cycle Cell Cycle Control
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