Regulation of growth, PSA/PAP and androgen receptor expression by 1 alpha,25-dihydroxyvitamin D3 in the androgen-dependent LNCaP cells.
The involvement of vitamin D in prostate carcinogenesis was investigated using the human prostatic LNCaP cells. Incubation of the LNCaP with 100 nM 1 alpha,25-dihydroxyvitamin D3 for 2 days resulted in a 30-40% suppression of cell growth, which was accompanied by a greater than 70% down-regulated expression of the proliferating cell nuclear antigen (PCNA). The intracellular and secreted forms of PSA showed a 2-fold increase following a 48 h culture in the presence of vitamin D3. The vitamin D3-elicited PSA increases were preceded by an induction of androgen receptor (AR) expression, as measured by Western blot analysis and by binding assays using [3H]R1881 as the ligand. These results are consistent with the hypothesis that the growth inhibitory effects of vitamin D3 is partially mediated through its ability to modulate PCNA expression. Moreover, vitamin D3 may effect increases in PSA expression indirectly by up-regulating androgen receptors.
Hsieh
T Y
TY
Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
Ng
C Y
CY
Mallouh
C
C
Tazaki
H
H
Wu
J M
JM
D000135:Acid Phosphatase / Q000096:biosynthesis*; D000728:Androgens / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D008297:Male; D015741:Metribolone / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis; D017430:Prostate-Specific Antigen / Q000096:biosynthesis*; D011471:Prostatic Neoplasms; D011944:Receptors, Androgen / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D000728:Androgens; D018809:Proliferating Cell Nuclear Antigen; D011944:Receptors, Androgen; D015741:Metribolone; D000135:Acid Phosphatase; D017430:Prostate-Specific Antigen; D002117:Calcitriol