Prostate cancer hormonal regulation

Hormones regulate many important bodily functions and are also associated with cancer. One of the first hints of the relationship of hormones to cancers was the observation that nuns had a greater incidence of breast cancer. This was naturally related to the nuns not having children and now we know that breast cancer may be hormone related. Since then there have been numerous studies on the use of birth control with cancer, childbirth, and most recently hormone replacement association with cancer. In males there is ongoing study of the hormones and prostate cancer. While it is clear that hormones and cancer are related, the exact characterization of this relationship is still unclear. 

Breast, prostate, testicular, and ovarian cancers are all considered hormonal malignancies. Sex hormones are known to affect the initiation or progression of these malignancies. However, all kallikreins are under sex steroid hormonal regulation. Taken together, kallikreins may represent downstream targets by which hormones affect the initiation or progression of such tumors. 

Rahman KM, Banerjee S, Ali S, Ahmad A, Wang Z, Kong D, Sakr WA (2009) 3,3 -Diin-dolylmethane enhances taxotere-induced apoptosis in hormone-refractory prostate cancer cells through survivin down-regulation. Cancer Res 69 4468 1475... 

Hormone Receptors. Certain types of cancer, mainly breast cancer, endometrial cancer, and prostate cancer, show a growth dependency on sexual hormones such as estradiol and testosterone [26]. As those cells overexpress hormone receptors, down-regulation of the hormone concentration is a powerful tool in the fight against those cancer types. Among the chemotherapeutics approved for treatment is tamoxifen [27, 28]. In recent years, also related complexes, that is, the ferrocifenes [29] were developed for that purpose. For detailed information on this class of molecules, please see Chapter 42. 

Over expression of tumor suppressor gene bcI-2 plays an important role in cellular resistance to apoptosis caused by various factors (77). Lin et al have shown that over expression of anti-apoptotic Bcl-2 and Bc1-Xl proteins may play a role in the development of resistance to cancer therapy 18). Functional over expression of Bcl-2 has been reported to confer an anti-apoptotic potential in a variety of cell types. The role of Bcl-2 in epithelial cell-cycle control and in interactions with other cell-cycle regulators is not clearly understood. Its expression has been correlated with the hormone- and chemo-resistant phenotype in advanced prostate cancer 19). Granville et al have shown that overexpression of Bcl-2 in HL-60 cells prevented apoptosis-related events including caspase 3 and 6 activation, poly (ADP-ribose) polymerase cleavage by photodynamic therapy (20). Over expression of HER2 in estrogen receptor (ER)-positive human breast tumors has been associated with resistance to endocrine therapy. 

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