Role of Posttranscriptional Processes in the Regulation of GlutathioneS-Transferase P1 Gene Expression in Human Breast Cancer Cells

Abstract

Human glutathioneS-transferase P1 (GSTP1) is normally expressed in estrogen receptor negative (ER−) but not receptor positive (ER+) cultured breast cancer cells. Previous results indicated that posttranscriptional mechanisms may contribute to this differential expression of GSTP1 (J. Biol. Chem.267, 10544–10550, 1992). Here, we have tested the hypothesis that differences in posttranscriptional processing of primary transcripts to mature mRNA or differences in mRNA stability influence the levels of GSTP1 in ER− versus ER+ breast cancer cells. We examined the expression both of the endogenousGSTP1gene and of uniquely designedGSTP1minigenes that were stably transfected into HS578T (ER−) and MCF7 (ER+) cells. In both cell lines,GSTP1transcripts are processed to mature, functional mRNAs. However, GSTP1 mRNA is considerably less stable in MCF7 than in HS578T cells. These results indicate that for a given level ofGSTP1gene transcription, differential mRNA stability will result in higher steady state levels of GSTP1 mRNA in ER−, HS578T than in ER+, MCF7 cells.