Stable expression of full length human androgen receptor in PC-3 prostate cancer cells enhances sensitivity to retinoic acid but not to 1alpha,25-dihydroxyvitamin D3.
BACKGROUND
PC-3 prostate cancer cell growth is inhibited by 1alpha,25-dihydroxyvitamin D(3) (1,25 D) and retinoids, but not to the same extent as the androgen receptor (AR) positive LNCaP prostate cancer cells. Previous reports suggest a role for AR in growth inhibition of LNCaP cells by 1,25 D and retinoids. PC-3 cells do not express AR. We therefore asked whether re-expression of AR would enhance the response of PC-3 cells to 1,25 D and retinoids.


METHODS
PC-3 cells were stably transfected with wild type human AR cDNA. Pooled cells expressing AR protein at levels comparable to LNCaP cells were used to analyze response to 1,25 D, retinoids, androgens, and anti-androgens.


RESULTS
AR re-expression in PC-3 cells restored response to androgens and anti-androgens, but growth inhibition by 1,25 D was not significantly altered. However, cells were sensitized to low levels of retinoids, and, in contrast to the parental PC-3 cells, sub-optimal levels of 1,25 D and retinoids caused additive growth inhibition.


CONCLUSIONS
Restoring AR expression and activity in PC-3 cells results in enhanced sensitivity to low levels of retinoids while the response to 1,25 D remains unaltered. Thus, the involvement of AR in prostate cancer growth inhibition by 1,25 D appears to be cell line specific.
Murthy
Shalini
S
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Marcelli
Marco
M
Weigel
Nancy L
NL
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000502:physiology; D014212:Tretinoin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000494:pharmacology*
C116441:2-methyl-1,25-dihydroxyvitamin D3; D000970:Antineoplastic Agents; D011944:Receptors, Androgen; D014807:Vitamin D; D014212:Tretinoin