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

Mol Cell Endocrinol. 1999 Oct 25;156(1-2):13-23. doi: 10.1016/s0303-7207(99)00151-3.

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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenovirus E1A Proteins / genetics
  • Adenovirus E1A Proteins / metabolism*
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Line, Transformed
  • Enhancer Elements, Genetic
  • Gene Expression Regulation*
  • Genes, Reporter
  • Genes, ras
  • Keratinocytes / metabolism*
  • Luciferases / genetics
  • Mice
  • Parathyroid Hormone / genetics
  • Parathyroid Hormone-Related Protein
  • Promoter Regions, Genetic*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / genetics*
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic

Substances

  • Adenovirus E1A Proteins
  • Ets1 protein, mouse
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Protein Isoforms
  • Proteins
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • Transcription Factors
  • Luciferases