What is prostate cancer? The prostate is a gland of the male reproductive system and can be found in most mammals. The prostate is located under the bladder and increases from the size of a walnut with age.
Prostate cancer begins when the cells of the prostate begin to divide uncontrollably. Most prostate cancers are adenocarcinomas, as they begin from gland cells. However other types of cancers can also occur in the prostate like sarcomas and carcinomas. Prostate cancer uses the TNM staging system to determine the stage of the cancer, this involves looking at the size of the initial tumour, if it has spread to lymph nodes and whether it has metastasised. |
Symptoms and Treatments
Prostate cancer is initially asymptotic so it can be hard to detect, which is why regular checks are suggested in high risk males. The risk of prostate cancer increases with age and cases of prostate cancer in men under 40 are rare, this may be related to the growth of the prostate with age. As the cancer advances symptoms include issues urinating (including blood in the urine), erectile dysfunction and pain in the hips, backs or anywhere else the cancer may have spread to.
Active surveillance is often the first form of treatment for prostate cancer patients. It involves monitoring the cancer regularly and starting treatment if and when the cancer begins to spread or cause symptoms. Once the cancer becomes dangerous radiotherapy, chemotherapy and other therapies are used to kill the cancerous cells. Some men may also choose to undergo a prostatectomy, which is surgery to remove the prostate, this carries its own risk and is only effective if the cancer is localised to the prostate.
Active surveillance is often the first form of treatment for prostate cancer patients. It involves monitoring the cancer regularly and starting treatment if and when the cancer begins to spread or cause symptoms. Once the cancer becomes dangerous radiotherapy, chemotherapy and other therapies are used to kill the cancerous cells. Some men may also choose to undergo a prostatectomy, which is surgery to remove the prostate, this carries its own risk and is only effective if the cancer is localised to the prostate.
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Role of RASSF1A
Ras Associated Domain Family 1A (RASSF1A) is a tumour suppressor gene located on chromosome 3 [1]. Ordinarily the RASSF1A protein acts in many cell growth control pathways and can help induce apoptosis or cell cycle arrest [2]. RASSF1A has been implicated in many cancers, including prostate cancer. In prostate cancer the gene undergoes epigenetic alterations which affects its expression [1, 3]. DNA methylation is the process of adding a methyl group to cytosine residue (when it is followed by a guanine) in DNA. Due to further mutations, over time clusters of CpG dinucleotides will form, these are known as GpG islands and are found to be hypermethylated in RASSF1A in prostate cancer [3].
One study showed RASSF1A to be hypermethylated within the promoter region of the gene in 96% of cell lines [3]. This inappropriate methylation leads to silencing of the gene, so the protein is not expressed and is often passed on in replication to daughter cells. With a tumour suppressor gene silenced it is easier for the cancer to grow and advance as the protein is not transcribed so it will not function as required.
One study showed RASSF1A to be hypermethylated within the promoter region of the gene in 96% of cell lines [3]. This inappropriate methylation leads to silencing of the gene, so the protein is not expressed and is often passed on in replication to daughter cells. With a tumour suppressor gene silenced it is easier for the cancer to grow and advance as the protein is not transcribed so it will not function as required.
References
https://www.cancer.org/cancer/prostate-cancer.html
seer.cancer.gov/statfacts/html/prost.html
http://www.cancerresearchuk.org/about-cancer/prostate-cancer
[1] Ge, YZ., Xu, LW., Jia, RP. et al. 2014. The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies. Tumour Biol. 35: 3881
[2] Donninger, H. Vos, M.D. & Clark, G.J. 2007. The RASSF1A tumour suppressor. Journal of Cell Science. 120: 3163-3172.
[3] Yegnasubramanian, S., Kowalski, J., Gonzalgo, M.L. et al. 2004. Hypermethylation of GpG islands in primary and metastatic human prostate cancer. Cancer Research. 64(6): 1975-1986.
seer.cancer.gov/statfacts/html/prost.html
http://www.cancerresearchuk.org/about-cancer/prostate-cancer
[1] Ge, YZ., Xu, LW., Jia, RP. et al. 2014. The association between RASSF1A promoter methylation and prostate cancer: evidence from 19 published studies. Tumour Biol. 35: 3881
[2] Donninger, H. Vos, M.D. & Clark, G.J. 2007. The RASSF1A tumour suppressor. Journal of Cell Science. 120: 3163-3172.
[3] Yegnasubramanian, S., Kowalski, J., Gonzalgo, M.L. et al. 2004. Hypermethylation of GpG islands in primary and metastatic human prostate cancer. Cancer Research. 64(6): 1975-1986.
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
Author
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Email
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Last Updated
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Kieran Neale
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10th May 2017
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