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Regulation of growth and epidermal growth factor receptor levels of LNCaP prostate tumor cells by different steroids
Author(s) -
Schuurmans Alex L.G.,
Bolt Joan,
Voorhorst Marleen M.,
Blankenstein Rien A.,
Mulder Eppo
Publication year - 1988
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910420622
Subject(s) - endocrinology , medicine , dihydrotestosterone , lncap , androgen receptor , epidermal growth factor , androgen , receptor , biology , testosterone (patch) , steroid hormone , growth factor , chemistry , hormone , prostate , prostate cancer , cancer
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.