An N-terminal splice variant of human Stat5a that interacts with different transcription factors is the dominant form expressed in invasive ductal carcinoma

Cancer Lett. 2014 Apr 28;346(1):148-57. doi: 10.1016/j.canlet.2013.12.030. Epub 2013 Dec 30.

Abstract

We have identified a new variant of human Stat5a, found at higher ratios to full-length Stat5a in invasive ductal carcinoma versus contiguous normal tissue. The variant, missing exon 5, inhibits p21 and Bax production and increases cell number. After prolactin stimulation, only full-length Stat5a interacts with the vitamin D and retinoid X receptors, whereas only Δ5 Stat5a interacts with activating protein 1-2 and specificity protein 1. Prolactin also oppositely regulates interaction of the two Stat5a forms with β-catenin. We propose that a change in splicing leading to upregulation of this new isoform is a pathogenic aspect of invasive ductal carcinoma.

Keywords: Breast cancer; Interaction with other signaling/transcription factors; Invasive ductal carcinoma; Splice variant; Stat5a.

Publication types

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

MeSH terms

  • Base Sequence
  • Blotting, Western
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Carcinoma, Ductal, Breast / genetics*
  • Carcinoma, Ductal, Breast / metabolism
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • Humans
  • Molecular Sequence Data
  • Protein Isoforms
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT5 Transcription Factor / genetics*
  • STAT5 Transcription Factor / metabolism
  • Signal Transduction
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transfection
  • Tumor Suppressor Proteins / genetics*
  • Tumor Suppressor Proteins / metabolism
  • Up-Regulation

Substances

  • Protein Isoforms
  • STAT5 Transcription Factor
  • STAT5A protein, human
  • Transcription Factors
  • Tumor Suppressor Proteins