Posters-Accepted Abstracts: J Cancer Sci Ther
Prostate cancer is a major health issue in westernized countries being considered a prototypical age-related, androgendependent tumor. However, data on the association between circulating androgens and prostate cancer are inconsistent and not compatible with the androgen/aging hypothesis. Furthermore, plasma androgen to estrogen ratio appears to decrease with age, suggesting that estrogens may have a role. Some studies suggest that circulating steroids cannot be considered representative of their intra-prostatic levels, as a consequence of expression and/or activity of steroid enzymes, including 17β hydroxyl steroid dehydrogenase, 5α-reductase, 3α/3βHSD and aromatase, eventually leading to a differential tissue accumulation of steroid derivatives having distinct biological activities. Furthermore, the time scale of prostate carcinogenesis and cancer progression usually spans 35-40 years or longer. Therefore, the timing for the carcinogenetic impact of androgen and/or estrogen on human prostate should be allocated back to 20-30 years (or earlier) prior to the clinical manifestation of disease, when serum androgens are higher and potentially relevant. There is consistent evidence that exposure of prostate cells to elevated estrogens in uterine or perinatal life (a process referred to as developmental estrogenization) may be responsible for permanent perturbations of prostate development that may eventually result in an increased propensity to develop precancerous or malignant lesions. One could speculate that developmental estrogenization induce changes in a pool of embryonic stem cells that may, in turn, generate a population of adult imprinted prostate stem cells having high susceptibility of developing cancer. Based on this evidence, a hypothetical model of prostate cancer development and progression is presented.