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Control of the Cell Cycle Cyclins and Checkpoints Control of the Cell Cycle Cell cycle checkpoints are used by the cell to monitor and regulate the progress of the cell cycle. Checkpoints prevent cell cycle progression at specific points, allowing verification of necessary phase processes and repair of DNA damage. The cell cannot proceed to the next phase until checkpoint requirements have been met. Several checkpoints are designed to ensure that damaged or incomplete DNA is not passed on to daughter cells. Two main checkpoints exist: the *G1/S checkpoint and the *G2/M checkpoint. G1/S transition is a rate-limiting step in the cell cycle and is also known as restriction point. http://outreach.mcb.harvard.edu/animations/checkpoints.swf Anchorage dependence Most animal cells will not divide unless they are in contact with a solid surface. Ex. If cells in a lab are suspended in a liquid they will rarely divide. However if the cells are poured onto a solid surface where they can attach, they begin dividing immediately. This may keeps cells that become separated from their normal surroundings from dividing inappropriately. Density-dependent inhibition a.k.a. contact inhibition Cell in a laboratory will only grow in a single layer and stop dividing when they touch one another. If some are removed from the middle, the cells will begin dividing again (analogous to a cut in your skin!) If stimulated to divide by adding growth factors, the cells will still only form a single layer but they will be smaller and more numerous. Normal cells will fill in a gap and then stop dividing… Cancer cells do not recognize contact inhibition and continue to divide. Cancer Uncontrolled Cell Division The Cell Cycle and Cancer Abnormal growth of cells is called a neoplasm Benign neoplasms are not cancerous Encapsulated (enclosed) Do not invade neighboring tissue or spread Malignant neoplasms are cancerous Not encapsulated Readily invade neighboring tissues, and lymph nodes which can carry the cancer cells to new locations. May also detach and lodge in distant places – metastasis Results from mutation of genes regulating the cell cycle Carcinogenesis – development of cancer Tends to be gradual May be years before cell is obviously cancerous Characteristics of Cancer Cells Lack differentiation Have abnormal nuclei Form tumors Mitosis controlled by contact with neighboring cells – contact inhibition Cancer cells have lost contact inhibition Undergo metastasis Original tumor easily fragments New tumors appear in other organs Undergo angiogenesis Formation of new blood vessels http://www.researchvegf.com/researchvegf/multimedia/in dex.m?video=vegffull&mov=VEGF_Angiogenesis_Full.mp4&wmv=VEGF_A ngiogenesis_Full.wmv Tumor angiogenesis — the ability to form new blood vessels – represents a critical step in tumor development through which the tumor establishes an independent blood supply, consequently facilitating tumor growth. Cancer Cells Versus Normal Cells Four groups of cancers Carcinomas: cancers that originate in the external or internal coverings of the body, such as the skin or the lining of the intestines. Sarcomas: cancers that arise in tissues that support the body, such as bone and muscle. Leukemias and Lymphomas: cancers of blood-forming tissues, such as bone marrow, spleen, and lymph nodes. Origins of Cancer: Oncogenes Mutations in DNA repair mechanisms Oncogenes Proto-oncogenes promote the cell cycle in various ways Tumor suppressor genes inhibit the cell cycle in various ways Both normally regulated in coordination with organism’s growth plan If either mutates, may lose control and become oncogene Telomeres Telomeres are six nucleotide sequences at the end of each chromosome in the nuclei of your cells. They are not genes, rather they protect the genetic information in the chromosome. When a cell divides, the DNA in the chromosome is reproduced except for the very tip of the chromosome. The telomeres sacrifice a small amount of the repeated sequences with each division and thus the telomere and the chromosome become slightly shorter with each division. Origins of Cancer:Telomerase Chromosomes normally have special material at each end called telomeres (end parts) These get shorter each cell division When they get very short The cell will no longer divide Telomerase is an enzyme that adds telomeres Mutations in telomerase gene: Keeps adding new telomeres Allow cancer cells to continually divide Telomerase High levels of telomerase activity are detected in embryonic stem cells and cancer cells; little or no telomerase activity is present in most mature, differentiated cell types. Functions of telomeres and telomerase appear to be important in cell division, normal development, and aging. Scientists and doctors have been attempting to target cancer through telomerase. Telomerase is one of the only constants between almost all types of cancers. Instead of hundreds of therapies for hundreds of types of cancers—we could be looking at one type of therapy for all types of cancers. Cancer Treatments Disrupt cell division Chemotherapy Often antimitotic drugs Some interfere with the spindle fibers Vinblastin: from the periwinkle flower, prevents the spindle from froming Taxol: from the Pacific yew, freezes the spindle after it forms Radiation Focused, high energy radiation Since cancer cells are dividing more rapidly than body cells at any given time, so radiation can disrupt cell division without seriously injuring the normal cells of the body. Future treatments? Nanotechnology! Blocking telemerase? This is a huge field of research with new technologies and treatments