Abstract
Experiments have been designed to investigate hormonal effects on the human prostatic carcinoma cell line LNCaP in the presence of complete foetal calf serum. At physiological concentrations (3.3 x 10(-9)M), several derivatives of 17 alpha-methyl-testosterone led to a significant reduction of cell proliferation, inhibition of colony formation in soft agar, change of morphology, induction of a prostate specific mRNA and down-regulation of c-myc RNA. Two different antiandrogens, hydroxyflutamide and cyproterone acetate, were capable of reversing the effects exerted by the synthetic androgens on growth properties. The proliferation rate of control cells devoid of androgen receptor was not inhibited by synthetic androgens. Our results indicate that the cellular androgen response mechanism of LNCaP cells is intact and that synthetic androgens elicit androgen receptor mediated suppression of the transformed phenotype. Rare cases of remission of prostatic cancer on androgen treatment have been reported. LNCaP cells may be a model of an uncommon class of prostatic cancer which responds favourably to androgen treatment.
Highlights
A number of cell lines of prostatic origin has been established (Stone et al, 1978; Kaighn et al, 1979; Horoszewicz et al, 1980)
In contrast to studies using delipidated foetal calf serum (FCS), we found no indication of androgen dependence of hormone responsive LNCaP cells
In complete FCS, synthetic androgens containing a 1 7amethyl-testosterone backbone consistently inhibit the proliferation of LNCaP cells at physiological concentrations, while the natural androgen DHT is effective ony at a 1,000fold higher concentration, and, does not achieve the same degree of inhibition as the synthetic compounds (Table I)
Summary
A number of cell lines of prostatic origin has been established (Stone et al, 1978; Kaighn et al, 1979; Horoszewicz et al, 1980). The LNCaP cell line (Horoszewicz et al, 1980) which retains functional properties of normal prostatic epithelial cells is regarded as the best-suited in vitro model of prostate cancer available. LNCaP cells synthesise at least three prostate specific proteins, i.e. prostate specific acid phosphatate (Horoszewicz et al, 1983; Schulz et al, 1985), prostate specific antigen (PSA; Schulz et al, 1988), and the antigen reactive with the monoclonal antibody KR-P8 (Raynor et al, 1984), and they contain an androgen receptor (Horoszewicz et al, 1983) which has recently been reported to carry a mutation in the steroid binding domain (Veldscholt et al, 1990b)
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