POSITIVE AND NEGATIVE REGULATIONS OF HUMAN PLATELET-ACTIVATING-FACTORRECEPTOR TRANSCRIPT-2 (TISSUE-TYPE) BY ESTROGEN AND TGF-BETA-1

We found that the expression of human platelet-activating factor recep tor (PAFR) gene is differentially regulated by estrogen and TGF-beta 1 . Primer extension analysis revealed that the levels of the PAFR trans cript 2 were increased by estrogen, but decreased by TGF-beta 1 in the human stomach cancer cell line (JR-St cells) which expressed both fun ctional endogenous PAFR transcript 1 (leukocyte-type) and transcript 2 (tissue-type). Both ligands did not affect the expression of intrinsi c PAFR transcript 1. Furthermore, the response elements to estrogen an d TGF-beta 1 in the PAFR promoter 2 were delineated by a transient exp ression assay using the chloramphenicol acetyltransferase (CAT) gene a s a reporter in this cell line. A negative response element for TGF-be ta 1 was mapped on the sequence from -90 bp to -81 bp, which has conse nsus sequence for TIE (TGF-beta 1 inhibitory element). Although consen sus estrogen response element (AGGTCAnnnTGACCT) is not present in this promoter, the entire sequence comprising two AGGTCA half motifs space d by 153 bp (from -257 bp to -93 bp) conferred weak but significant es trogen responsiveness. Thus, through these elements in the PAFR promot er 2, estrogen and TGF-beta 1 may regulate the PAFR gene to achieve a tissue-specific expression. (C) 1994 Academic Press, Inc.