Osanai Makoto, Lee Gang-Hong
Department of Pathology, Kochi University School of Medicine, Nankoku, Kochi 783-8505, Japan.
Oncol Rep. 2016 Nov;36(5):2755-2762. doi: 10.3892/or.2016.5072. Epub 2016 Sep 5.
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.
维生素D通过调节影响细胞增殖、分化和凋亡的基因表达，在组织稳态中发挥关键作用。维生素D 24-羟化酶CYP24A1在维生素D靶组织中发挥作用，降解维生素D的激素形式。关于CYP24A1表达失调的现有知识支持其作为推定癌基因的候选资格。在此，我们发现，组成型CYP24A1表达的抑制使靶细胞对凋亡的敏感性增加，从而抑制乳腺癌细胞的非锚定依赖性生长。此外，CYP24A1敲低后维生素D代谢的抑制显著降低了体内肿瘤生长。这些数据为CYP24A1在乳腺癌细胞中的促生存和刺激致癌作用提供了大量证据。
