{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:19:15Z","timestamp":1791235155800,"version":"4.1.0"},"reference-count":88,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2007,9,4]],"date-time":"2007-09-04T00:00:00Z","timestamp":1188864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2007,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prostate cancer is the commonest non\u2010skin cancer in men. Incidence and mortality rates of this tumor vary strikingly throughout the world. Although several factors have been implicated to explain this remarkable variation, lifestyle and dietary factors may play a dominant role, with sex hormones behaving as intermediaries between exogenous factors and molecular targets in development and progression of prostate cancer. Human prostate cancer is generally considered a paradigm of androgen\u2010dependent tumor; however, estrogen role in both normal and malignant prostate appears to be equally important. The association between plasma androgens and prostate cancer remains contradictory and mostly not compatible with the androgen hypothesis. Similar evidence apply to estrogens, although the ratio of androgen to estrogen in plasma declines with age. Apart from methodological problems, a major issue is to what extent circulating hormones can be considered representative of their intraprostatic levels. Both nontumoral and malignant human prostate tissues and cells are endowed with key enzymes of steroid metabolism, including 17\u03b2hydroxysteroid dehydrogenase (17\u03b2HSD), 5\u03b2\u2010reductase, 3\u03b1\/3\u03b2HSD, and aromatase. A divergent expression and\/or activity of these enzymes may eventually lead to a differential prostate accumulation of steroid derivatives having distinct biological activities, as it occurs for hydroxylated estrogens in the human breast. Locally produced or metabolically transformed estrogens may differently affect proliferative activity of prostate cancer cells. Aberrant aromatase expression and activity has been reported in prostate tumor tissues and cells, implying that androgen aromatization to estrogens may play a role in prostate carcinogenesis or tumor progression. Interestingly, many genes encoding for steroid enzymes are polymorphic, although only a few studies have supported their relation with risk of prostate cancer. In animal model systems estrogens, combined with androgens, appear to be required for the malignant transformation of prostate epithelial cells. Although the mechanisms underlying the hormonal induction of prostate cancer in experimental animals remain uncertain, there is however evidence to support the assumption that long term administration of androgens and estrogens results in an estrogenic milieu in rat prostates and in the ensuing development of dysplasia and cancer. Both androgen and estrogen have been reported to stimulate proliferation of cultured prostate cancer cells, primarily through receptor\u2010mediated effects. As for estrogens, the two major receptor types, ER\u03b1 and ER\u03b2, are expressed in both normal and diseased human prostate, though with a different cellular localization. Since these two receptors are different in terms of ligand binding, heterodimerization, transactivation, and estrogen response element activity, it is likely that an imbalance of their expression may be critical to determine the ultimate estrogen effects on prostate cancer cells. In prostate cancer, ER\u03b2 activation appears to limit cell proliferation directly or through ER\u03b1 inhibition, and loss of ER\u03b2 has been consistently associated with tumor progression. Several splicing variants of both ER\u03b1 and ER\u03b2 exist. Little is known about their expression and function in the human prostate, although reciprocal regulation and interaction with gene promoter both warrant further investigation. In summary, although multiple consistent evidence suggests that estrogens are critical players in human prostate cancer, their role has been only recently reconsidered, being eclipsed for years by an androgen\u2010dominated interest. J. Cell. Biochem. 102: 899\u2013911, 2007. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcb.21529","type":"journal-article","created":{"date-parts":[[2007,9,4]],"date-time":"2007-09-04T15:47:16Z","timestamp":1188920836000},"page":"899-911","source":"Crossref","is-referenced-by-count":126,"title":["Estrogen and prostate cancer: An eclipsed truth in an androgen\u2010dominated scenario"],"prefix":"10.1002","volume":"102","author":[{"given":"Giuseppe","family":"Carruba","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2007,9,4]]},"reference":[{"key":"e_1_2_8_2_1","volume-title":"Cancer facts and figures 2007","author":"American Cancer Society","year":"2007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1677\/erc.1.00800"},{"key":"e_1_2_8_4_1","first-page":"169","article-title":"A prospective, population\u2010based study of androstenedione, estrogens, and prostatic 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