MAPK inhibition by 1alpha,25(OH)2-Vitamin D3 in breast cancer cells. Evidence on the participation of the VDR and Src

The Journal of Steroid Biochemistry and Molecular Biology
Ana M RossiRicardo Boland

Abstract

1alpha,25-Dihydroxyvitamin D(3) [1alpha,25(OH)(2)D(3)], the hormonally active form of Vitamin D(3), has been shown to be a potent negative growth regulator of breast cancer cells both in vitro and in vivo. 1alpha,25(OH)(2)D(3) acts through two different mechanisms. In addition to regulating gene transcription via its specific intracellular receptor (Vitamin D receptor, VDR), 1alpha,25(OH)(2)D(3) induces, rapid, non-transcriptional responses involving activation of transmembrane signal transduction pathways. The mechanisms that mediate the antiproliferative effects of 1alpha,25(OH)(2)D(3) in breast cancer cells are not fully understood. Particularly, there is no information about the early non-genomic signal transduction effectors modulated by the hormone. The present study shows that 1alpha,25(OH)(2)D(3) rapidly inhibits serum induced activation of ERK-1 and ERK-2 MAP kinases. The non-receptor tyrosine kinase Src is involved in the pathway leading to activation of ERK 1/2 by serum. Furthermore, 1alpha,25(OH)(2)D(3) increases the tyrosine-phosphorylated state of Src as well as it inhibits its kinase activity and induces the association of the VDR with Src. These data suggest that 1alpha,25(OH)(2)D(3) inhibits MAPK by inactivatin...Continue Reading

References

Nov 1, 1992·Endocrine Reviews·M R Walters
May 1, 1992·Journal of Cellular Biochemistry·A R de Boland, I Nemere
Feb 16, 1995·Nature·T Pawson

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Citations

Oct 20, 2015·Critical Reviews in Clinical Laboratory Sciences·Surojit SarkarVandana Kalia
May 12, 2017·Journal of Animal Physiology and Animal Nutrition·J R VazquezA G Avila
Dec 13, 2005·Journal of Neurochemistry·Darja ObradovicTheo Rein

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