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 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 endogenous GSTP1 gene and of uniquely designed GSTP1 minigenes that were stably transfected into HS578T (ER-) and MCF7 (ER+) cells. In both cell lines, GSTP1 transcripts 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 of GSTP1 gene transcription, differential mRNA stability will result in higher steady state levels of GSTP1 mRNA in ER-, HS578T than in ER+, MCF7 cells.