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Vitamin D Autocrine System and Cancer

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Biologic Effects of Light 2001

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Abstract

Epidemiological and biochemical evidence strongly implicates a role for the active form of vitamin D, 1α,25-dihydroxyvitamin D [1α,25(OH)2D], in the growth and differentiation of human breast, colon and prostate cells. Recently, our laboratory demonstrated the presence of mRNA and enzyme activity for 25-hydroxyvitamin D-1α-hydroxylase (1α-OHase), the enzyme responsible for the synthesis of 1α,25(OH)2D, in human cancer cells derived from those tissues. We further demonstrated a marked decrease in 1α-OHase activity in the primary cultures and cell lines of prostate cancer cells, compared to those found in the primary cultures of normal prostate cells. Transient or stable transfection of LNCaP prostate cancer cells with 1α-OHase cDNA greatly increased the 1α-OHase enzyme activity, and thereby their cellular response to the antiproliferative activity of 25(OH)D. These findings suggest that, by synthesizing la,25(OH)2D within the cell, the enzyme may play an autocrine role in modulating the proliferation and differentiation of breast, colon and prostate cells. Thus, higher circulating concentrations of 25(OH)D may be necessary for the extra-renal 1α-OHase to work at its maximum capacity to produce an adequate amount of 1α,25(OH)2D in tissues such as the breast, colon and prostate to regulate cell growth and protect them from becoming malignant. This may explain why people who live closer to the equator are less likely to die from cancers of the breast, colon and prostate.

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Authors and Affiliations

  1. Vitamin D, Skin and Bone Research Laboratory, Section of Endocrinology, Department of Medicine, Boston University Medical Center, 02118, Boston, MA, USA

    Tai C. Chen & Michael F. Holick

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  1. Tai C. Chen
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  1. Boston, Massachusetts, USA

    Michael F. Holick

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Chen, T.C., Holick, M.F. (2002). Vitamin D Autocrine System and Cancer. In: Holick, M.F. (eds) Biologic Effects of Light 2001. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0937-0_23

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  • DOI: https://doi.org/10.1007/978-1-4615-0937-0_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5313-3

  • Online ISBN: 978-1-4615-0937-0

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