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Lecture 9

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Biochemistry 2280A
Christopher Brandl

Cancer ● Cancer is the leading cause of death in NorthAmerica ● Strikes victims of all ages ● Cancer will become even more prevalent as the population ages Molecular Basis of Cancer ● Cancer is characterization by genetic and biochemical defects ● Biochemistry and molecular biology provide avenues for cures ● Tumor types: ○ Adenoma (Benign) ■ encapsulated thus the cancer cells do not go anywhere and can be easily removed ○ Adenocarcinoma (Malignant) ■ are not contained and thus tend to spread ● Metastasis is the cells of a tumour spreading through the blood to other regions of the body ○ The tumour can eventually break through the basal lamina and into the blood vessel, allowing migration to other regions, where it breaks through the blood vessels into other tissues and grow TumourAngiogenesis ● Sometimes, there are small micro tumours that cannot grow due to not enough nutrients being available for growth ● However, tumours have a method of attracting blood vessels to them and allow transfer of nutrients from the blood vessels, thus allowing growth of the tumour ○ this is called angiogenesis ○ technically, if we can control the blood vessels, we can control tumour growth How do we know that cancer is a Genetic Disease ● Susceptibility to cancer can be inherited ● Also, DNAdamaging agents can cause cancer (UV rays, x-rays, chemical mutagens) ○ these agents damage DNAand mutations in the DNAtend to cause cancer WHat are some of theAvoidable Causes of Cancer? ● Agents that cause DNAdamage; radiation, chemical mutagens etc. ● Chemicals that cause cells to divide: tumour promoters - asbestos ○ these don’t cause DNAdamage, just cause cells to divide which promotes cancer ● Certain viruses such as certain types of Hepatitis (liver cancer), HPV (cervical cancer and others), and HIV ● 30% of all cancers can be attributed to smoking (90% of lung cancer) ● Cigarette smoke contains 69 chemicals that are known to cause cancer Cancer risk increases with age. Why? ● Asingle mutation is not sufficient to cause cancer ● Tumour progression involves multiple successive rounds of mutation and selection (the tumour is selected to grow faster) ● At each round, the descendent cell acquires another mutation allowing to grow faster or in abnormal places; natural selection gone ‘bad’ ● Note, most cancers derive from a single abnormal cell ● First mutation allows a cell to grow more quickly ● Second mutation may allow the cells to grow in absence of the basal lamina ● The third mutation may allow the cells to penetrate through the basal lamina etc. Properties of Cancer Cells ● Cancer cells will divide in the absence of growth factors ○ normal cells divide only when they are signalled to divide; cancer cells will grow in the absence of these signals ● Cancer cells are immortal ○ they do not respond to signals that normally trigger cell death; most cells, after enough replication, will be signalled to die however cancer cells have lost these signals ● Cancer cells have lost cell cycle control ○ Remember there are 4 parts to the cell cycle: G , S1 G , a2d Mitosis ■ G is1preparation for replication ■ S is the replication of the chromosomes ■ G is2the double check before mitosis ■ Mitosis is the actual cell division ○ There are certain checkpoints throughout the cell cycle ■ G ch1ckpoint is to check for cell size, nutrients, growth factors and DNA damage to make sure it is okay before replication (s phase) ● if there is any damage, cycle won’t continue to s phase until it is fixed ■ G ch2ckpoint is before mitosis to check for cell size and make sure it is okay to replicate and divide the cell; checks for chromosomes being okay and if the cell is okay ● if there is damage, cell division won’t occur ■ Finally, the spindle assembly checkpoint in the mitosis phase occurs to make sure that the chromosomes are aligned correctly and that the spindles are working ● Cancer cells will not look at any of these checkpoints; they do not have any of these safety mechanisms and thus will divide regardless of how much DNAdamage is there ○ the DNAdamage accumulates as the cell cycle continues without fixing any of the damage ● As a result, cancer cells are genetically unstable: ○ there are more point mutations ○ copy number variation ○ major chr
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