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CYP24A1‐induced vitamin D insufficiency promotes breast cancer growth
Author(s) -
Osanai Makoto,
Ono Yusuke,
Takasawa Kumi,
Takasawa Akira
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00570
Subject(s) - cyp24a1 , vitamin d and neurology , calcitriol receptor , cancer research , gene knockdown , cancer , oncogene , breast cancer , biology , apoptosis , medicine , microbiology and biotechnology , endocrinology , cell cycle , genetics
Vitamin D plays a critical role in the maintenance of 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. In our presentation, we demonstrate that the suppression of constitutive CYP24A1 expression by CYP24A1 ‐specific shRNA 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 . Since these data provide substantial evidence for a pro‐survival and stimulatory oncogenic effect of CYP24A1 in breast carcinoma cells, we will discuss the potential feasibility of CYP24A1‐inhibitory cancer therapies.