Interleukin-1? mediates the antiproliferative effects of 1,25-dihydroxyvitamin D3 in prostate progenitor/stem cells.

ABSTRACT: Vitamin D(3) is a promising preventative and therapeutic agent for prostate cancer, but its implementation is hampered by a lack of understanding about its mechanism of action. Upon treatment with 1?,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3), vitamin D(3)], the metabolically active form of vitamin D(3), adult prostate progenitor/stem cells (PrP/SC) undergo cell-cycle arrest, senescence, and differentiation to an androgen receptor-positive luminal epithelial cell fate. Microarray analyses of control- and vitamin D(3)-treated PrP/SCs revealed global gene expression signatures consistent with induction of differentiation. Interestingly, one of the most highly upregulated genes by vitamin D(3) was the proinflammatory cytokine interleukin-1? (IL-1?). Systems biology analyses supported a central role for IL-1? in the vitamin D(3) response in PrP/SCs. siRNA-mediated knockdown of IL-1? abrogated vitamin D(3)-induced growth suppression, establishing a requirement for IL-1? in the antiproliferative effects of vitamin D(3) in PrP/SCs. These studies establish a system to study the molecular profile of PrP/SC differentiation, proliferation, and senescence, and they point to an important new role for IL-1? in vitamin D(3) signaling in PrP/SCs.

SUBMITTER: Maund SL 

PROVIDER: S-EPMC3148300 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature