Abstract
Studies were performed to determine whether ARP-1, which is an orphan receptor of the steroid receptor superfamily, inhibits basal activity of the human placental lactogen (hPL) promoter and the increase in hPL promoter activity in response to the receptors for thyroid hormone (TR) and retinoic acid (RAR). Co-transfection of an ARP-1 expression vector into BeWo choriocarcinoma cells, along with an expression vector containing 1.2 kb of the hPL promoter coupled to a CAT reporter gene, resulted in a dose-dependent inhibition of basal CAT activity. In addition, ARP-1 inhibited the stimulation of CAT activity by RAR alpha and TR beta expression vectors. Mobility shift assays demonstrated that ARP-1 binds specifically to a composite steroid response element on the hPL promoter that confers retinoic acid and T3 responsiveness. The results implicate an inhibitory role for ARP-1 in the regulation of hPL gene expression and strongly suggest that hPL gene expression is regulated, at least in part, by the interaction of stimulatory and inhibitory members of the steroid receptor superfamily.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Base Sequence
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COUP Transcription Factor II
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COUP Transcription Factors
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Cell Differentiation
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Cell Line
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Chloramphenicol O-Acetyltransferase / biosynthesis
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Choriocarcinoma
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DNA Primers
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DNA-Binding Proteins / metabolism*
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Gene Expression Regulation, Neoplastic*
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Genes, Reporter
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Humans
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Kinetics
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Oligodeoxyribonucleotides
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Placental Lactogen / biosynthesis*
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Placental Lactogen / genetics
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Polymerase Chain Reaction / methods
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Promoter Regions, Genetic*
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RNA, Messenger / biosynthesis
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Receptors, Retinoic Acid / biosynthesis
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Receptors, Retinoic Acid / metabolism
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Receptors, Steroid / metabolism
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Receptors, Thyroid Hormone / biosynthesis
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Receptors, Thyroid Hormone / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / metabolism
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Repressor Proteins / metabolism*
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Retinoic Acid Receptor alpha
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Transcription Factors*
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Transcription, Genetic
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Transfection
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Trophoblasts / cytology
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Tumor Cells, Cultured
Substances
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COUP Transcription Factor II
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COUP Transcription Factors
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DNA Primers
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DNA-Binding Proteins
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NR2F2 protein, human
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Oligodeoxyribonucleotides
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RARA protein, human
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RNA, Messenger
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Receptors, Retinoic Acid
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Receptors, Steroid
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Receptors, Thyroid Hormone
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Recombinant Proteins
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Repressor Proteins
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Retinoic Acid Receptor alpha
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Transcription Factors
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Placental Lactogen
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Chloramphenicol O-Acetyltransferase