Disruption of vitamin D receptor-retinoid X receptor heterodimer formation following ras transformation of human keratinocytes.

The Journal of Biological Chemistry
C SolomonR Kremer

Abstract

A partial resistance to the growth inhibitory influence of 1, 25-dihydroxyvitamin D3 is apparent when immortalized keratinocytes are transformed by the ras oncogene. The vitamin D receptor (VDR) was isolated, analyzed, and found to be identical in normal, immortalized, and ras-transformed keratinocytes. Subsequently, nuclear extracts from immortalized and ras-transformed keratinocytes were analyzed in gel mobility shift assays utilizing labeled vitamin D response elements or thyroid hormone response elements. A specific protein.DNA complex that was shown to contain VDR using an anti-VDR antibody was identified in both types of extracts; however, the addition of an anti-retinoid X receptor (RXR) antibody identified RXR in the complex of both normal and immortalized keratinocyte cell extracts, but not in ras-transformed keratinocytes. Furthermore, transfection of ras-transformed keratinocytes with wild-type human RXRalpha rescued VDR.RXR and thyroid hormone receptor.RXR complexes as demonstrated by a supershift in the presence of the anti-RXR antibody. Both cell lines were found to express RXRalpha message in equal amounts. Western blot analysis revealed that RXRalpha protein from ras-transformed keratinocytes was indistinguishab...Continue Reading

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Citations

Jun 1, 2001·The Journal of Steroid Biochemistry and Molecular Biology·D GoltzmanR Kremer
Jan 10, 2001·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·C SolomonR Kremer
Jun 15, 2011·Molecular and Cellular Endocrinology·JoEllen Welsh
Sep 4, 2008·Journal of Cellular Biochemistry·Carly M Kemmis, JoEllen Welsh
Jan 25, 2005·The Journal of Steroid Biochemistry and Molecular Biology·Donna M Peehl, David Feldman
Oct 3, 2008·The Journal of Nutritional Biochemistry·Laura M TaberDorothy Teegarden
Sep 18, 2013·The Journal of Steroid Biochemistry and Molecular Biology·Mark B MeyerJ Wesley Pike
Aug 28, 2004·The Journal of Biological Chemistry·Ramesh NarayananNancy L Weigel
Apr 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Marielle Gascon-BarréAntonio Nanci
Sep 25, 2019·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Chen YuanKimmie Ng

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