The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells

Yongfeng Shang, Craig R. Baumrucker, Michael H. Green

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Retinoic acid receptor-β (RARβ) and signal transducer and activator of transcription 1 (STAT1) are important mediators of the antiproliferative and apoptotic actions of retinoids and cytokines/growth factors, respectively. Expression of both RARβ and STAT1 is lost in most breast cancer cell lines hut it can be induced by retinoids in estrogen receptor-positive cells. We investigated a possible functional connection between these two mediators and present evidence supporting RARβ as a tumor suppressor. First, by using different receptor-selective retinoids, we demonstrated that RARβ induction in MCF-7 cells by all-trans-retinoic acid (atRA) was associated with the activation of STAT1 gene transcription. The direct involvement of RARβ in atRA-induced STAT1 gene activation was further demonstrated by showing that transfection with an anti-sense RARβ construct blocked atRA-induced STAT1 expression in MCF-7 cells whereas introduction of a sense-RARβ construct resulted in STAT1 induction by atRA in MDA-MB 231 cells. In addition, we showed that STAT1 was phosphorylated/activated under atRA treatment of MCF-7 cells; this process required the involvement of RARβ and protein synthesis. STAT1 phosphorylation/activation was accompanied by increased tyrosine kinase activity that was not due to the activation of JAK1, JAK2 or Tyk 2, suggesting the possible involvement of an unidentified tyrosine kinase.

Original languageEnglish (US)
Pages (from-to)6725-6732
Number of pages8
JournalOncogene
Volume18
Issue number48
DOIs
StatePublished - Nov 18 1999

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Fingerprint Dive into the research topics of 'The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells'. Together they form a unique fingerprint.

Cite this