Regulation of prostate growth

Infrequent involvement of p53 gene mutations in the tumourigenesis of Japanese prostate cancer

“…Approximately 4,000 and 28,000 men die each year in the UK (Davies & Eaton, 1991) and the United States (Carter & Coffey, 1990), respectively. It is now the fourth and second leading cause of cancer death among men in both of these countries.…”

“…Various abnormalities have been reported in the molecular genetics of prostate cancer, such as overexpression of growth factors that include the fibroblast growth factor, transforming growth factor-1B families, transforming growth factor-o and epidermal growth factor (Davies & Eaton, 1991;see Thompson, 1990 for review). Elevated activities of proto-oncogenes such as ras and myc has also been detected in prostate cancer L. Eaton, 1991; see Thompson, 1990 for reviews).…”

“…Prostatic adenocarcinoma is the fourth and second most common cause of cancer death among men in the UK (Davies & Eaton, 1991) and United States (Silverberg et al, 1990) (Waterhouse et al, 1982). Recent advances in molecular genetics of other prevalent tumours, such as colorectal (Vogelstein et al, 1988), bladder (Tsai et al, 1990), lung and breast cancers (Callahan & Cambell, 1989), indicate multiple genetic alterations by activation of oncogenes (see Bishop, 1991 for reviews) and, more importantly, the inactivation of tumour suppressor genes (see Marshall, 1991 (Carter et al, 1990c (Kaighn et al, 1979) and DU-145 (Stone et al, 1978), were obtained from the American Tissue Type Collection and used as positive controls.…”

Microarray coupled to quantitative RT–PCR analysis of androgen-regulated genes in human LNCaP prostate cancer cells

“…The importance of AR in male development is shown by the androgen insensitivity syndromes characterized by mutations in the AR gene (Gottlieb et al, 2004). The prostate is a prototypical androgen-dependent organ (Cunha et al, 1987;Davies and Eaton, 1991) and prostate cancer, which has become the most commonly diagnosed cancer in males in the western world and is the second leading cause of male cancer death, is androgen-dependent for its growth (Carter and Coffey, 1990;McConnell, 1991). Therefore, treatment is directed at inhibiting prostate cancer growth by suppressing the action of the endogenous androgen or its production.…”

5α-Androstane-3α,17β-diol activates pathway that resembles the epidermal growth factor responsive pathways in stimulating human prostate cancer LNCaP cell proliferation

“…5a-Dihydrotestosterone (5a-DHT), the most potent androgen in the prostate with high affinity toward the androgen receptor (AR; K d ¼ 10 À10 M), 1 modulates androgen responsive gene (ARG) expression, 2,3 and has been implicated in the development of prostatic diseases including benign prostatic hyperplasia (BPH) and prostate cancer (PCa). 4 Within the prostate, 5a-DHT can be reduced to weaker androgens, including 5a-androstane-3a,17b-diol (3a-diol) and 5a-androstane3b,17b-diol (3b-diol), through the action of 3a-hydroxysteroid dehydrogenase (3a-HSD) and 3b-HSD, respectively. Of these two pathways, prostatic 3a-HSDs play dominant roles in 5a-DHT reduction.…”