Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: A role for basal promoter and Ets-1 site

John Foley, John J. Wysolmerski, Caterina Missero, Connie S. King, William M. Philbrick

Research output: Contribution to journalArticle

14 Scopus citations

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. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)13-23
Number of pages11
JournalMolecular and Cellular Endocrinology
Volume156
Issue number1-2
DOIs
StatePublished - Oct 25 1999

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Keywords

  • Coactivator
  • E1A
  • Keratinocyte
  • PTHrP
  • Repression

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

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