CYP24A1-induced vitamin D insufficiency promotes breast cancer growth.
Vitamin D plays a critical role in tissue homeostasis by regulating the expression of genes affecting cell proliferation, differentiation, and apoptosis. The vitamin D 24-hydroxylase CYP24A1 functions in vitamin D target tissues to degrade the hormonal form of vitamin D. Existing knowledge regarding dysregulated CYP24A1 expression supports its candidacy as a putative oncogene. Here, we found that the suppression of constitutive CYP24A1 expression conferred target cells with increased susceptibility to apoptosis and consequently inhibited anchorage-independent growth in breast carcinoma cells. In addition, suppression of vitamin D metabolism following knockdown of CYP24A1 significantly reduced tumor growth in vivo. These data provide substantial evidence for a pro-survival and stimulatory oncogenic effect of CYP24A1 in breast carcinoma cells.
Department of Pathology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
Makoto
M
Osanai
Department of Pathology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
Gang-Hong
GH
Lee
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D014807:Vitamin D / Q000235:genetics* / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase / Q000096:biosynthesis* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
D014807:Vitamin D; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase