Caveolin expression is decreased following androgen deprivation in human prostate cancer cell lines.
BACKGROUND
Increased expression of caveolin has been associated with prostate cancer progression. In a mouse reconstitution model of prostate cancer, expression of caveolin was inversely related to androgen sensitivity: androgen independent clones had high caveolin expression; low caveolin expression was associated with sensitivity to androgen withdrawal. In contrast, several independent observations support the hypothesis that caveolin functions as a tumor suppressor.


METHODS
Caveolin expression was studied by Western blot analysis and/or immunohistochemistry in three androgen-sensitive human prostate cancer cell lines LNCaP, LAPC-4 and LAPC-9, and following acute and chronic androgen deprivation, and in benign prostate epithelial cells. Expression of caveolin, androgen receptor (AR) and prostate specific antigen (PSA) was also examined 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, but no tumors formed in wildtype LNCaP-bearing animals. Caveolin expression was decreased in every androgen-deprived LNCaP clone and following 150 days of androgen deprivation in LAPC-4. Caveolin expression by LAPC-9 was very low. Following exposure to dihydrotestosterone in vitro, caveolin and PSA expression increased within three days in the androgen-deprived clones of LNCaP. 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 activity.
The James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
B R
BR
Pflug
R E
RE
Reiter
J B
JB
Nelson
D000818:Animals; D015153:Blotting, Western; D002369:Castration / Q000662:veterinary; D051242:Caveolin 1; D022461:Caveolins; D013196:Dihydrotestosterone / Q000378:metabolism*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D011467:Prostate / Q000166:cytology / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D011897:Random Allocation; D014407:Tumor Cells, Cultured
C495540:CAV1 protein, human; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D013196:Dihydrotestosterone