Ras activation is associated with vitamin D receptor mRNA instability in HC11 mammary cells.
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.
Rozenchan
Patricia B
PB
Disciplina de Oncologia, Departamento de Radiologia, Faculdade de Medicina da Universidade de São Paulo, 01246-903 São Paulo, SP, Brazil.
Folgueira
Maria A A K
MA
Katayama
Maria L H
ML
Snitcovsky
Igor M L
IM
Brentani
M Mitzi
MM
D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005260:Female; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D009154:Mutation / Q000235:genetics; D020871:RNA Stability / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics; D018631:ras Proteins / Q000378:metabolism*
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D018631:ras Proteins