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Vitamin D Regulates Human Ectocervical Epithelial Cell Proliferation and Insulin-Like Growth Factor-Binding Protein-3 Level¹

^a Departments of Physiology and Biophysics, ^b Dermatology, ^c Reproductive Biology, ^d Biochemistry, and ^e Environmental Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4970 ^f Retinoid Research, Departments of Chemistry and ^g Biology, Allergan Pharmaceuticals, Irvine, California 92713

The differentiation status of the cervical epithelial cell has an important influence on responsiveness to estrogens and progestins. Several agents, including glucocorticoids and retinoids, are known to influence cervical cell differentiation. However, the effects of vitamin D have not been examined. Vitamin D is known to regulate cell proliferation and gene expression in a variety of epithelial cells. In the present study we investigated the ability of 125-dihydroxyvitamin D₃ (D3) to regulate cell proliferation and expression of insulin-like growth factor-binding protein-3 (IGFBP-3) in human ectocervical epithelial cells. ECE16-1, a non-tumorigenic cervical cell line, was growth inhibited by D3 with maximal inhibition at 1000 nM. IGFBP-3 levels increased in parallel with the growth inhibition. IGFBP-3 levels were half-maximally increased at approximately 10-100 nM and maximally increased (10- to 30-fold) at 1000 nM D3. These studies show that vitamin D regulates cervical epithelial cell gene regulation and cell proliferation and that IGFBP-3 may be an in vivo marker of vitamin D action in the cervix.

¹ This work was supported by a grant from the American Institute for Cancer Research (R.L.E.) and by Allergan Pharmaceuticals (R.L.E.) and utilized the facilities of the Skin Diseases Research Center of Northeast Ohio (NIH, AR39750).

² Correspondence: Richard L. Eckert, Department of Physiology/Biophysics, Rm E532, Case Western Reserve University School of Medicine, 2109 Adelbert Road, Cleveland, OH 44106-4970. FAX: 216 368 5586; rle2{at}po.cwru.edu

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