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Objective: Understand the biological basis of cancer Summary Cell division occurs through the cell cycle Tightly regulated with several checkpoints Cancer occurs because cell growth becomes unregulated The process is called oncogenesis Associated with two families of genes Suppressor genes Proto-oncogenes/ Activator genes Several factors are known to damage cells to cause them to have their growth unregulated Inherited Chemical Physical Infectious
G0- "Growth 0" phase. The cell is at rest, no division is occurring (lots of cells are like this in the body, as they are terminally differentiated) G1- "Growth 1" phase. The cell prepares to divide, BECAUSE it's received an instruction to divide. As a result, it will now synthesise proteins and enzymes required for division The instruction can be from a hormone, growth factor, a change in local conditions etc. S- "Synthesis" phase. The cell will now replicate DNA. This is the longest stage clocking in at 6-8 hours. G2- "Growth 2" phase. The cell has two copies of DNA, and it will now produce proteins required for mitosis to occur. Takes 2-3 hours. M- "Mitosis" phase. The cell will now split, taking one copy of the DNA, to
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M- "Mitosis" phase. The cell will now split, taking one copy of the DNA, to produce two identical cells. This is the shortest phase, clocking in at 1 hour. The cell will now return to G0 phase, and can re-enter the cycle if stimulated. Normally, we would expect the number of dying cells to equal the number of cells created to keep the number of cells in the body constant A homeostatic mechanism exists in the body to keep things under control Cells will be killed off due to apoptosis over time While other cells will be triggered to grow to replace these dying cells If the homeostatic mechanism fails, then we get cancer. So the cell cycle is tightly regulated to stop this from happening
Oncogenesis
An important fact is one mutation is not enough to cause cancer Remember: the cell cycle is tightly regulated, so the cell has quite a few barriers which it needs to overcome to become cancerous Normally, these mutations will be prevented by the checkpoints put in place But if the checkpoints are non-functional (either inherited or mutated), then it's much easier for these mutations to occur, so it's easier for the cell to become cancerous REMEMBER: normally a person will carry two copies of the gene, both must be broken to get cancer ('dominant' gene, so hetrozygous people are still at
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be broken to get cancer ('dominant' gene, so hetrozygous people are still at higher risk of getting cancer as a result) Because the cell needs multiple mutations to become cancerous, cancer is a disease which is concentrated in the elderly If you live long enough, by chance you will accumulate enough mutations Also, there are two main groups where mutations will cause cancer, as they are important for regulation of cell growth: Suppressor genes Activator genes (proto-oncogenes) Suppressor genes will work to prevent cancer, so these should be kept ON p53 is again an important suppressor gene, as it contains apoptosis genes BRCA is an important suppressor gene as it is involved in double stranded DNA repair If BRCA is mutated, the incidence of breast cancer shoots through the roof Anything inhibiting growth, such as growth regulator genes are important Contact inhibition genes- normally these will stop cells from dividing if they are in contact with each other, as it indicates there's no space to grow. Activator genes are also called proto-oncogenes, as normally they are not cancerous, but if mutated, will cause cancer. Therefore, to prevent cancer, these should be kept 'INACTIVATED' (not completely off, normal body function might need them, like healing) Angiogenic genes are very important in tumours, as the tumour must be able to get a blood supply set up to grow properly. Otherwise the tumours will be small and most likely unsuccessful. Some genes will allow cells to escape immune survellance, or be immunosuppressive Others will help them survive outside the tumour, which allows distant metastasis to occur (surviving outside the original tumour is quite difficult)
Why? Because p53 can trigger apoptosis and ruin their plans Human Papillomavirus (HPV) and Epsein-Barr virus Cause increased division, which leads to more chances of being mutated and causing cancer This is probably why hepatitis B and C cause liver cancer Insertion into oncogenic gene Yeah this can only end badly Seen by retroviruses (can enter the host's DNA) like HTLV-1 or HIV
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