Action, localization and structure-function relationship of growth factors and their receptors in the prostate

Abstract

Whereas the direct action of sex steroids, namely of androgens, on prostate cell division was questioned as early as in the 1970s, and remains so, the interest in prostatic growth factors (GFs) is rather recent but has expanded tremendously in the last five years. This lag period can be partly explained by the fact that, at the time, androgen receptors had just been discovered, and newly developed hormonal regimens or strategies to treat patients with prostate carcinoma (PCa) or epithelioma had generated great enthusiasm and hopes in the medical and scientific community. Another point to consider was the difficulty in maintaining prostate tissues in organ cultures and the relative novelty of culturing prostate epithelial cells in monolayers. Failures of sex steroids to elicit a direct positive response on prostate cell divisionin vitro, as seenin vivo, were interpreted as resulting from inappropriate models or culture conditions. However, the increasing number of reports confirming the lack of mitogenic activity of sex steroidsin vitro, coupled with the powerful mitogenic activity of GFs displayed in other systems, the discovery of GF receptors (GF-Rs), and the elucidation of their signalling pathways showing sex steroid receptors as potential substrates of GF-activated protein kinases gradually led to an increased interest in the putative role of GFs in prostate physiopathology. Of utmost importance was the recognition that hormone refractiveness was responsible for PCa progression, and for the poor outcome of patients with advanced disease under endocrine therapies. This problem remains a major issue and it raises several key questions that need to be solved at the fundamental and clinical levels.