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Gene Signatures of 1,25‐Dihydroxyvitamin D 3 Exposure in Normal and Transformed Mammary Cells
Author(s) -
Simmons Katrina M.,
Beaudin Sarah G.,
Narvaez Carmen J.,
Welsh JoEllen
Publication year - 2015
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25129
Subject(s) - calcitriol receptor , cancer research , biology , skbr3 , cancer cell , telomerase reverse transcriptase , cell culture , galectin 1 , microbiology and biotechnology , telomerase , cancer , gene , vitamin d and neurology , endocrinology , genetics , human breast
To elucidate potential mediators of vitamin D receptor (VDR) action in breast cancer, we profiled the genomic effects of its ligand 1,25‐dihydroxyvitamin D 3 (1,25D) in cells derived from normal mammary tissue and breast cancer. In non‐transformed hTERT‐HME cells, 483 1,25D responsive entities in 42 pathways were identified, whereas in MCF7 breast cancer cells, 249 1,25D responsive entities in 31 pathways were identified. Only 21 annotated genes were commonly altered by 1,25D in both MCF7 and hTERT‐HME cells. Gene set enrichment analysis highlighted eight pathways (including senescence/autophagy, TGFβ signaling, endochondral ossification, and adipogenesis) commonly altered by 1,25D in hTERT‐HME and MCF7 cells. Regulation of a subset of immune ( CD14, IL1RL1, MALL, CAMP, SEMA6D, TREM1, CSF1, IL33, TLR4 ) and metabolic ( ITGB3, SLC1A1, G6PD, GLUL, HIF1A, KDR, BIRC3 ) genes by 1,25D was confirmed in hTERT‐HME cells and similar changes were observed in another comparable non‐transformed mammary cell line (HME cells). The effects of 1,25D on these genes were retained in HME cells expressing SV40 large T antigen but were selectively abrogated in HME cells expressing SV40 + RAS and in MCF7 cells. Integration of the datasets from hTERT‐HME and MCF7 cells with publically available RNA‐SEQ data from 1,25D treated SKBR3 breast cancer cells enabled identification of an 11‐gene signature representative of 1,25D exposure in all three breast‐derived cell lines. Four of these 11 genes ( CYP24A1, CLMN, EFTUD1 , and SERPINB1 ) were also identified as 1,25D responsive in human breast tumor explants, suggesting that this gene signature may prove useful as a biomarker of vitamin D exposure in breast tissue. J. Cell. Biochem. 116: 1693–1711, 2015. © 2015 Wiley Periodicals, Inc.