Ras activation is associated with Vitamin D receptor mRNA instability in HC11 mammary cells

• Published in: The Journal of steroid biochemistry and molecular biology Vol. 92; no. 1; pp. 89 - 95
• Main Authors: Rozenchan, Patricia B., Folgueira, Maria A.A.K., Katayama, Maria L.H., Snitcovsky, Igor M.L., Brentani, M. Mitzi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-09-2004; Elsevier Science
• Subjects: 3' Untranslated Regions - genetics; Animals; Biological and medical sciences; Cells, Cultured; DNA Mutational Analysis; Enzyme Activation; Farnesyltransferase inhibitor; Female; Fundamental and applied biological sciences. Psychology; Mammary cells; Mammary Glands, Animal - cytology; Mammary Glands, Animal - metabolism; Mice; mRNA stability; Mutation - genetics; ras Proteins - metabolism; Receptors, Calcitriol - genetics; RNA Stability - physiology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Transcription, Genetic - genetics; VDR transcriptional rate; Vertebrates: endocrinology; Vitamin D receptor; Mammary cells; Farnesyltransferase inhibitor; Vitamin D receptor; VDR transcriptional rate; mRNA stability; Vitamin D; Enzyme; Transferases; Activation; Farnesyl-diphosphate farnesyltransferase; Biological receptor
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2004.05.007

HC11, a spontaneously immortalized murine mammary lineage maintains features of normal cells while HC11 H-ras transformed cells (HC11 ras) are tumorigenic. Ras transformation is associated with a lower Vitamin D receptor (VDR) mRNA content. Our goal was to investigate the mechanism underlying VDR mRNA differences between these cells. Although the VDR transcriptional rate measured by run-on assays did not differ between the cells, our data suggested a pos transcriptional mechanism involving higher VDR mRNA degradation in HC11 ras cells which was not due to mutations in its 3′-UTR region since sequences of mRNA obtained from HC11 and HC11 ras cells were identical. Treatment of HC11 ras cells with a farnesyltransferase inhibitor, which prevents ras activation, causing an enhancement of VDR mRNA levels, indicating an association between the ras signaling pathway and VDR mRNA instability. The present work suggests that the decreased mRNA levels in HC11 ras cells might in part be due to an early loss of stability.