Clinical Significances
For clinical significances, expression of cyclin D1/p16/pRb play a critical role in tumorigenesis. However, when protein p16 is overexpressed, it leads to cervical cancer (p16 overexpression secondary to the functional inactivation of pRb by human papillomavirus E7 protein). In the case of cervical cancer PRB is functionally inactivated by HPV oncoproteins and that results in p16 overexpression. In addition to that, overexpression of the protein p16 is a useful diagnostic tool for cervical cancer laboratory screening. Many recent and previous immunohistochemical studies have clearly demonstrated that p16 is strongly expressed in almost all cervical cancers. Many people mistakenly take the fact that the low expression of protein p16 in the cell as a free condition of cervical cancer however it is not always true. Protein p16 regulates cell proliferation and pRb acts as a negative regulator of protein p16. It was also shown that p16 is involved in the regulation of the cellular life span and accumulates in senescent cells. Some studies also reported that transcriptional silencing of the p16 promoter by hypermethylation as a dominant mechanism of inactivation of the tumor suppressor in head and neck squamous cell carcinoma. It is believed that excesse of cyclin D and cyclin E is produced in breast cancer cells. A possible therapy in cancer is to by blocking cyclins and CDK’s activates. the only possible way of inactivating the CDKs is through the inhibitor protein p16. In the p16/cyclin D1/cdk4/pRb cell cycle regulatory cascade, the correlation between pRb and p16 is believed to be obvious in various cancer types. Thus, loss of p16, overexpression of D-cyclins and loss of RB have similar effects on G1 cell cycle progression, and may represent a common pathway to tumorigenesis.
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