Prolactin signals via Stat5 and Oct-1 to the proximal cyclin D1 promoter

Mol Cell Endocrinol. 2005 Jul 15;239(1-2):45-53. doi: 10.1016/j.mce.2005.04.006.

Abstract

Prolactin (PRL) modulates proliferation in the mammary gland and other tissues, in part through inducing transcription of cyclin D1, a key regulator of G(1) phase cell cycle progression. We showed previously that PRL, via Jak2, induces binding of Stat5 to a distal GAS site (GAS1) in the cyclin D1 promoter. However, full promoter activity requires additional regions, and in this paper we explored PRL-induced activity at sites other than GAS1. We defined a second PRL-responsive region spanning -254 to -180 that contains a second GAS site (GAS2) and an Oct-1 binding site. Although mutational analysis indicated independence from GAS2, proximal promoter activity remained Stat5-dependent, suggesting alternative mechanisms. EMSA showed that Oct-1 binds the -254 to -180 region and that PRL decreased Oct-1 binding, leading to increased PRL-responsiveness of the proximal cyclin D1 promoter in multiple cell lines. This suggests a role for Oct-1 in PRL-dependent control of cyclin D1 transcription.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Cyclin D1 / biosynthesis*
  • Cyclin D1 / genetics
  • DNA-Binding Proteins / metabolism*
  • Gene Expression Regulation / drug effects*
  • Gene Expression Regulation / genetics
  • Humans
  • Janus Kinase 2
  • Milk Proteins / metabolism*
  • Mutation
  • Octamer Transcription Factor-1
  • Prolactin / pharmacology*
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology*
  • Protein Binding / genetics
  • Protein Binding / physiology
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • STAT5 Transcription Factor
  • Signal Transduction / drug effects*
  • Signal Transduction / genetics
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • Milk Proteins
  • Octamer Transcription Factor-1
  • POU2F1 protein, human
  • Proto-Oncogene Proteins
  • STAT5 Transcription Factor
  • Trans-Activators
  • Transcription Factors
  • Cyclin D1
  • Prolactin
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Janus Kinase 2