A Role for Interleukin-1 Alpha in the 1,25 Dihydroxyvitamin D(3) Response in Mammary Epithelial Cells

Breast cancer is the most common non-cutaneous malignancy in American women, and better preventative strategies are needed. Epidemiological and laboratory studies point to vitamin D(3) as a promising chemopreventative agent for breast cancer. Vitamin D(3) metabolites induce anti-proliferative effects in breast cancer cells in vitro and in vivo, but few studies have investigated their effects in normal mammary epithelial cells. We hypothesized that 1,25(OH)(2)D(3), the metabolically active form of vitamin D(3), is growth suppressive in normal mouse mammary epithelial cells. In addition, we have previously established a role for the cytokine interleukin-1 alpha (IL1α) in the anti-proliferative effects of 1,25(OH)(2)D(3) in normal prostate cells, and so we hypothesized that IL1α is involved in the 1,25(OH)(2)D(3) response in mammary cells. Evaluation of cell viability, clonogenicity, senescence, and induction of cell cycle regulators p21 and p27 supported an anti-proliferative role for 1,25(OH)(2)D(3) in mammary epithelial cells. Furthermore, 1,25(OH)(2)D(3) increased the intracellular expression of IL1α, which was necessary for the anti-proliferative effects of 1,25(OH)(2)D(3) in mammary cells. Together, these findings support the chemopreventative potential of vitamin D(3) in the mammary gland and present a role for IL1α in regulation of mammary cell proliferation by 1,25(OH)(2)D(3).