Regulation of growth and epidermal growth factor receptor levels of LNCaP prostate tumor cells by different steroids

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Abstract
The growth of LNCaP cells, derived from a lymph-node carcinoma of the human prostate, was stimulated by different hormones. Optimal growth (3- to 4-fold increase in DNA content per culture versus controls) was observed at 0.1 nm R1881 (a synthetic androgen), 1 nm progesterone or 10 nm estradiol. Triamcinolone acetonide had no effect. Dihydrotestosterone maximally stimulated cell growth at 10 nM. When the culture medium was changed 4 times in 6 days instead of twice, optimal growth was observed at 1 nm dihydrotestosterone. This indicates that a rapid metabolism of dihydrotestosterone influenced growth response. LNCaP cells contained considerable amounts of androgen receptors (920 fmol/mg cytosol protein) while progestagen, estrogen and glucocorticoid receptors were absent. The affinity of steroids for the androgen receptor decreased in the order of: R1881 (relative binding affinity: 100.0) > dihydrotestosterone (67.7) > progesterone (29.4) > testosterone (23.8) > estradiol (4.3) > triamcinolone acetonide (< 0.1). Effects on cell growth of these steroids paralleled their affinity for the androgen receptor. The number of EGF receptors per cell increased in a dose-dependent manner upon treatment with various hormones. Again the amount of steroid needed for maximal effects reflected the affinity of the steroid for the androgen receptor. An approximately 2-fold increase in EGF receptor number was observed within 24 hr and before an increase in growth could be detected. Actinomycin-D and cycloheximide inhibited the hormonally induced increase in EGF receptor numbers.