Caveolin expression is decreased following androgen deprivation in human prostate cancer cell lines

BACKGROUND. Increased expression of caveolin has been associated with prost ate cancer progression. In a mouse reconstitution model of prostate cancer, expression of caveolin was inversely related to androgen sensitivity: andr ogen independent clones had high caveolin expression; low caveolin expressi on was associated with sensitivity to androgen withdrawal. In contrast, sev eral independent observations support the hypothesis that caveolin function s as a tumor suppressor. METHODS, Caveolin expression was studied by Western blot analysis and/or im munohistochemistry in three androgen-sensitive human prostate cancer cell l ines LNCaP, LAPC-4 and LAPC-9, and following acute and chronic androgen dep rivation, and in benign prostate epithelial cells. Expression of caveolin, androgen receptor (AR) and prostate specific antigen (PSA) was also examine d after reintroduction of androgen. RESULTS. LNCaP grown continuously under androgen-depleted conditions for 6 to 42 months produced several androgen-independent and tumorigenic clones: tumors formed in 13/15 castrate and 7/15 intact male athymic nu/nu mice, bu t no tumors formed in wildtype LNCaP-bearing animals. Caveolin expression w as decreased in every androgen-deprived LNCaP clone and following 150 days of androgen deprivation in LAPC-4. Caveolin expression by LAPC-9 was very l ow. Following exposure to dihydrotestosterone in vitro, caveolin and PSA ex pression increased within three days in the androgen-deprived clones of LNC aP. Benign prostate epithelial cells have high caveolin expression. CONCLUSIONS. Unlike the mouse reconstitution model of prostate cancer, the pattern of caveolin expression in benign prostatic epithelium and androgen- sensitive human prostate cancer is consistent with tumor suppressive activi ty. (C) 1999 Wiley-Liss, Inc.