Abstract
PTHrP gene expression was evaluated in a murine keratinocyte line, Pam 212K, transformed with E1A and ras. We found that the 12S-E1A oncogene, with or without ras transformation, markedly reduced PTHrP mRNA expression. Using transient transfection assays, we found that the 12S isoform repressed activity from a 5'PTHrP-driven reporter gene. E1A-induced repression of PTHrP reporter constructs appears to be mediated by sequences within minimal promoter region. The 13S-E1A isoform did not repress PTHrP reporter gene activity, and a 13S-deletion mutant that lacked the repressor domains activated a subset of reporter constructs. Mutation of an Ets-1 binding site upstream of the basal promoter substantially decreased activation of reporter constructs by this 13S-deletion mutant. These findings suggest that the E1A oncoprotein may serve as a model for both activation and repression of PTHrP gene expression.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenovirus E1A Proteins / genetics
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Adenovirus E1A Proteins / metabolism*
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Animals
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Base Sequence
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Binding Sites
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Cell Line, Transformed
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Enhancer Elements, Genetic
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Gene Expression Regulation*
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Genes, Reporter
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Genes, ras
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Keratinocytes / metabolism*
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Luciferases / genetics
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Mice
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Parathyroid Hormone / genetics
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Parathyroid Hormone-Related Protein
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Promoter Regions, Genetic*
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Proteins / genetics*
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-ets
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RNA, Messenger / genetics
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Transcription Factors / metabolism
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Transcription, Genetic
Substances
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Adenovirus E1A Proteins
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Ets1 protein, mouse
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Parathyroid Hormone
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Parathyroid Hormone-Related Protein
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Protein Isoforms
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Proteins
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Proto-Oncogene Protein c-ets-1
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-ets
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RNA, Messenger
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Transcription Factors
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Luciferases