Positive and negative regulations of human platelet-activating factor receptor transcript 2 (tissue-type) by estrogen and TGF-beta 1.
We found that the expression of human platelet-activating factor receptor (PAFR) gene is differentially regulated by estrogen and TGF-beta 1. Primer extension analysis revealed that the levels of the PAFR transcript 2 were increased by estrogen, but decreased by TGF-beta 1 in the human stomach cancer cell line (JR-St cells) which expressed both functional endogenous PAFR transcript 1 (leukocyte-type) and transcript 2 (tissue-type). Both ligands did not affect the expression of intrinsic PAFR transcript 1. Furthermore, the response elements to estrogen and TGF-beta 1 in the PAFR promoter 2 were delineated by a transient expression assay using the chloramphenicol acetyltransferase (CAT) gene as a reporter in this cell line. A negative response element for TGF-beta 1 was mapped on the sequence from -90 bp to -81 bp, which has consensus sequence for TIE (TGF-beta 1 inhibitory element). Although consensus estrogen response element (AGGTCAnnnTGACCT) is not present in this promoter, the entire sequence comprising two AGGTCA half motifs spaced by 153 bp (from -257 bp to -93 bp) conferred weak but significant estrogen responsiveness. Thus, through these elements in the PAFR promoter 2, estrogen and TGF-beta 1 may regulate the PAFR gene to achieve a tissue-specific expression.
Mutoh
H
H
Department of Biochemistry, Faculty of Medicine, University of Tokyo, Japan.
Kume
K
K
Sato
S
S
Kato
S
S
Shimizu
T
T
D001482:Base Composition; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016384:Consensus Sequence; D017931:DNA Primers; D004958:Estradiol / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008969:Molecular Sequence Data; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013274:Stomach Neoplasms; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D016212:Transforming Growth Factor beta; C039351:platelet activating factor receptor; D004958:Estradiol