Anti-proliferative action of vitamin D in MCF7 is still active after siRNA-VDR knock-down

• Type: Article in International Scientific Journal
• Date: 2009

Authors

Schmitt F (Author) FMUP

Journal

Title: BMC Genomics

Vol. 10

Final page: 499

ISSN: 1471-2164

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 35 Citations

Scopus - 44 Citations

Scientific classification

FOS: Medical and Health sciences > Other medical sciences

Other information

Authenticus ID: P-003-EZH

DOI: 10.1186/1471-2164-10-499

Abstract (EN): Background: The active form of Vitamin D, 1,25-dihydroxyvitamin D(3) (1,25D), has strong antiproliferative effects, yet the molecular mechanisms underneath this effect remain unclear. In contrast, the molecular mechanism of 1,25D for the regulation of calcium homeostasis has principally been resolved, demonstrating a pivotal role for the vitamin D receptor (VDR). Results: We first addressed the question whether the anti-proliferative effects of 1,25D are influenced by VDR. Knockdown of VDR by siRNA did not affect the anti-proliferative effects of 1,25D in MCF7 breast cancer cells. This unanticipated finding led us to take an alternative approach using genome wide screens to study the molecular mechanisms of 1,25D in proliferation. For that purpose, four independently developed and stable 1,25D resistant MCF7 cell lines were analyzed. Array CGH identified a copy number alteration in a region of 13.5 Mb at chromosome 11q13.4-14.1 common to all four 1,25D resistant cell lines. Expression arrays revealed that no single gene was differentially expressed between the sensitive and resistant cells, but multiple membrane receptor signaling pathways were altered in the 1,25D resistant cell lines. Importantly, in the genome wide experiments neither VDR, CYP24A1 nor other known vitamin D signaling pathway genes were associated with 1,25D resistance. Conclusion: In conclusion, siRNA and genome wide studies both suggest that the antiproliferative effects of 1,25D in MCF7 breast tumor cell lines do not rely on classical Vitamin D pathway per se.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11