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Analysis of vitamin D‐regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays
Author(s) -
Krishnan Aruna V.,
Shinghal Rajesh,
Raghavachari Nalini,
Brooks James D.,
Peehl Donna M.,
Feldman David
Publication year - 2003
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20006
Subject(s) - lncap , biology , microarray analysis techniques , gene expression , dna microarray , prostate cancer , gene expression profiling , androgen , cancer research , regulation of gene expression , gene , cell growth , microbiology and biotechnology , endocrinology , cancer , genetics , hormone
BACKGROUND 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] exerts growth inhibitory, pro‐differentiating, and pro‐apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH) 2 D 3 ‐regulated gene expression in the LNCaP human prostate cancer cells. METHODS mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH) 2 D 3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real‐time PCR assays. RESULTS 1,25(OH) 2 D 3 most substantially increased the expression of the insulin‐like growth factor binding protein‐3 ( IGFBP‐3 ) gene. Our analysis also revealed several novel 1,25(OH) 2 D 3 ‐responsive genes. Interestingly, some of the key genes regulated by 1,25(OH) 2 D 3 are also androgen‐responsive genes. 1,25(OH) 2 D 3 also down‐regulated genes that mediate androgen catabolism. CONCLUSIONS The putative 1,25(OH) 2 D 3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell–cell and cell–matrix interactions, DNA repair, and inhibition of metastasis. The up‐regulation of IGFBP‐3 gene has been shown to be crucial in 1,25(OH) 2 D 3 ‐mediated inhibition of LNCaP cell growth. 1,25(OH) 2 D 3 regulation of androgen‐responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH) 2 D 3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti‐cancer effects of 1,25(OH) 2 D 3 may lead to better approaches to the prevention and treatment of prostate cancer. © 2004 Wiley‐Liss, Inc.