Effect of culture conditions on androgen sensitivity of the human prostatic cancer cell line LNCaP.
Several effects of androgens on LNCaP-FGC prostate tumor cells showed a biphasic pattern. Stimulation of growth and inhibition of secretion of prostatic acid phosphatase (PAP) was observed at low androgen concentrations (below 1 nM of the synthetic androgen R1881), and inhibition of growth and stimulation of PAP secretion was observed at higher concentrations. In contrast, prostate specific antigen (PSA) secretion did not show this biphasic response pattern. Comparable effects were found for two sublines of the LNCaP-FGC cells: an early (passage 20, androgen-dependent) and relatively late (passage 70, androgen-sensitive) passage of the cells. Culturing of both sublines in the presence of a high concentration of androgens (10 nM R1881) resulted initially in a decrease in growth rate, but the cells started to proliferate within 3 weeks. These cells became less sensitive to androgens, lost their biphasic response pattern, and showed reduced androgen receptor levels. Three weeks after removal of the excess of androgens, the passage 70 cells regained a biphasic growth response to androgens. Culture in medium without steroids but with EGF resulted in a decrease of both androgen sensitivity and androgen receptor level. In conclusion, rapid changes of the androgen sensitivity and receptor level of the LNCaP cells occurred under the influence of culture conditions. These changes were partly reversible and, therefore, were most likely due to adaptation of the cells.
Langeler
E G
EG
Department of Endocrinology and Reproduction, Erasmus University, Rotterdam, The Netherlands.
van Uffelen
C J
CJ
Blankenstein
M A
MA
van Steenbrugge
G J
GJ
Mulder
E
E
D000135:Acid Phosphatase / Q000378:metabolism; D000728:Androgens / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects*; D003470:Culture Media / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000378:metabolism; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000187:drug effects*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000728:Androgens; D003470:Culture Media; D011944:Receptors, Androgen; D000135:Acid Phosphatase; D017430:Prostate-Specific Antigen