ROLE OF POSTTRANSCRIPTIONAL PROCESSES IN THE REGULATION OF GLUTATHIONE-S-TRANSFERASE P1 GENE-EXPRESSION IN HUMAN BREAST-CANCER CELLS

Human glutathione S-transferase P1 (GSTP1) is normally expressed in es trogen receptor negative (ER-) but not receptor positive (ER+) culture d breast cancer cells. Previous results indicated that posttranscripti onal mechanisms may contribute to this differential expression of GSTP 1 (J. Biol. Chem. 267, 10544-10550, 1992). Here, we have tested the hy pothesis 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 endogenous GSTP1 gene and of uniquely desi gned GSTP1 minigenes that were stably transfected into HS578T (ER-) an d MCF7 (ER+) cells. In both cell lines, GSTP1 transcripts are processe d to mature, functional mRNAs. However, GSTP1 mRNA is considerably les s stable in MCF7 than in HS578T cells. These results indicate that for a given level of GSTP1 gene transcription, differential mRNA stabilit y will result in higher steady state levels of GSTP1 mRNA in ER-, HS57 8T than in ER+, MCF7 cells. (C) 1997 Academic Press.