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 division in vitro, as seen in 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 steroids in 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.

Androgen ablation promotes neuroendocrine cell differentiation in dog and human prostate

“…Although, further studies are necessary to establish underlying mechanisms, a change in cell phenotype or serotonin-expression level rather than NE cell death is conceivable. This is in line with the prostate stem cell concept, whereby pluripotent intermediate cells act as progenitors of other subtypes [2,[50][51][52][53]. This is depicted in Figure 4, where a modified version of the model proposed by Bui et al [53] is presented and shows the divergent growth and differentiation patterns of epithelial cells, according to the hormonal milieu.…”

Neuroendocrine differentiation and the bombesin/gastrin-releasing peptide family of neuropeptides in the progression of human prostate cancer

“…However, it is clear that, in androgen-independent cancer, other factors are important. It is now evident that polypeptide hormones, such as epidermal, fibroblast, and transforming growth factors (EGF, FGF, and TFG, respectively), play a significant role in regulating the proliferation of prostatic cells [32]. In addition to these proteins, neuropeptides comprise another family of potential, but less well-studied, growth factors.…”

“…Of these, bombesin/GRP has received great attention as growth factors in normal and malignant tissues. In addition to their neuroregulatory effects, bombesin/GRP has proved to be a potent in vitro and in vivo mitogen and has been implicated in the pathogenesis of various human malignancies including lung, breast, colon, and recently prostate [9][10][11][12][13][14][32][33][34][35].…”

Increased Expression of FGF-8 Isoforms and FGF Receptors in Human Premalignant Prostatic Intraepithelial Neoplasia Lesions and Prostate Cancer

“…ibroblast growth factors (FGFs) and their receptors have been suggested to be involved in the progression of prostate cancer (reviewed in [Russell et al, 1998] and [Chevalier et al, 1996]). FGF-8 was originally cloned from SC-3 mouse mammary carcinoma cells and classified as an androgen-induced growth factor (Tanaka et al, 1992).…”