| First Author | Maund SL | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 15 | Pages | 5276-86 |
| PubMed ID | 21653679 | Mgi Jnum | J:174221 |
| Mgi Id | MGI:5052217 | Doi | 10.1158/0008-5472.CAN-10-2160 |
| Citation | Maund SL, et al. (2011) Interleukin-1{alpha} Mediates the Antiproliferative Effects of 1,25-Dihydroxyvitamin D3 in Prostate Progenitor/Stem Cells. Cancer Res 71(15):5276-86 |
| abstractText | 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 1alpha,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-1alpha (IL-1alpha). Systems biology analyses supported a central role for IL-1alpha in the vitamin D(3) response in PrP/SCs. siRNA-mediated knockdown of IL-1alpha abrogated vitamin D(3)-induced growth suppression, establishing a requirement for IL-1alpha 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-1alpha in vitamin D(3) signaling in PrP/SCs. Cancer Res; 71(15); 5276-86. (c)2011 AACR. |
