Volume 40, Number 1, 72-76, DOI: 10.1134/S0026893306010110

Calcitriol induces transcription of the placental transforming growth factor β gene in prostate cancer cells via an androgen-independent mechanism

N. Yu. Nazarova, G. I. Chikhirzhina and P. Tuohimaa

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Abstract

Calcitriol (1α,25-dihydroxycholecalciferol) suppresses the growth of prostate cancer cells. Growth suppression of hormone-sensitive LNCaP prostate cancer cells by calcitriol is believed to depend on androgens, but the mechanisms of the interactions between the calcitriol-and androgen-dependent signaling pathways is unclear. A previous search for calcitriol-responsive genes in LNCaP cells with cDNA microarrays has shown that calcitriol regulates the expression of the gene for the placental transforming growth factor β (PTGF-β), which suppresses prostate cancer cell proliferation. A study was made of whether expression of the PTGF-β gene is regulated by 5α-dihydrotestosterone and whether induction of this gene by calcitriol is androgen-dependent. Quantitative PCR showed that 5α-dihydrotestosterone increases the level of the PTGF-β mRNA. Neither 5α-dihydrotestosterone nor the antiandrogen Casodex affected the calcitriol-induced level of the PTGF-β mRNA. It was assumed that calcitriol stimulates production of PTGF-β independently of 5α-dihydrotestosterone and that its effect on prostate cancer cell growth is partly mediated by an androgen-independent mechanism.

Key words  calcitriol - 5α-dihydrotestosterone - placental transforming growth factor β - prostate cancer cells - quantitative polymerase chain reaction - gene expression - mRNA

Original Russian Text © N.Yu. Nazarova, G.I. Chikhirzhina, P. Tuohimaa, 2006, published in Molekulyarnaya Biologiya, 2006, Vol. 40, No. 1, pp. 84–89.

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