Abstract
We have investigated the possibility of a direct regulatory effect of gonadotrophin releasing hormone (GnRH) analogues on prostatic cancer cell growth. Here we report high affinity binding (Kd = 50 nM) of a GnRH analogue resulting in biphasic growth modulation of the human androgen-sensitive prostatic cancer cell line LNCaP. In contrast, the human androgen-insensitive prostatic cancer cell line DU145 showed low-affinity (Kd = 10 microM) binding without any biological response to the GnRH analogue. A GnRH-specific radioimmunoassay demonstrated GnRH-like immunoreactivity in the concentrated culture medium from both cell lines. Seventy-six human benign and malignant tumours were assayed following surgical resection. Nineteen of 22 (86%) malignant tumours and 49 of 54 (91%) benign tumours, exhibited high affinity GnRH-analogue binding. Fourteen of 19 (74%) malignant tumours and 17 of 49 (35%) benign tumours exhibiting high affinity binding contained GnRH-like immunoreactivity, suggesting that this system may be involved in prostatic epithelial cell growth in vivo.
Highlights
This present study explored the direct effects of gonadotrophin releasing hormone (GnRH) analogues on prostatic cancer cells in culture and in vivo
The LNCaP cells showed high affinity binding of buserelin with 50% inhibition obtained at 50 nM concentration of unlabelled peptide
A Scatchard plot of the same data indicated a single class of binding sites with Kd = 40 nM (Figure 3)
Summary
The human androgen-sensitive prostatic cancer cell line LNCaP (isolated from lymph node metastasis; Horoszewicz et al, 1983) and the human androgen-insensitive prostatic cell line DU145 (isolated from brain metastasis) were obtained from the American Type Culture Collection. Cultures were maintained in exponential growth in RPMI 1640 medium containing 10% charcoal stripped fetal calf serum and 5 fig ml-I insulin. The fetal calf serum used in cell culture medium was treated with dextran and charcoal to remove steroids. Charcoal 0.25% and dextran-T70 0.025% were added to the serum, which was heated at 56'C for 2 h and centrifuged at 4,000 r.p.m. for O min. The pellet was discarded, serum was filtered through 0.4 ltm filters and Correspondence: J.
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