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 journalArticle

30 Citations (Scopus)

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

Fingerprint

STAT1 Transcription Factor
Retinoic Acid Receptors
Tretinoin
Breast Neoplasms
MCF-7 Cells
Retinoids
Protein-Tyrosine Kinases
Estrogen Receptors
Transcriptional Activation
Transfection
Intercellular Signaling Peptides and Proteins
Phosphorylation
Cytokines
Cell Line

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Shang, Yongfeng ; Baumrucker, Craig R. ; Green, Michael H. / The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells. In: Oncogene. 1999 ; Vol. 18, No. 48. pp. 6725-6732.
@article{e1e85cdb6982450895b302cb4a78de7d,
title = "The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells",
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.",
author = "Yongfeng Shang and Baumrucker, {Craig R.} and Green, {Michael H.}",
year = "1999",
month = "11",
day = "18",
doi = "10.1038/sj.onc.1203084",
language = "English (US)",
volume = "18",
pages = "6725--6732",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "48",

}

The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells. / Shang, Yongfeng; Baumrucker, Craig R.; Green, Michael H.

In: Oncogene, Vol. 18, No. 48, 18.11.1999, p. 6725-6732.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The induction and activation of STAT1 by all-trans-retinoic acid are mediated by RARβ signaling pathways in breast cancer cells

AU - Shang, Yongfeng

AU - Baumrucker, Craig R.

AU - Green, Michael H.

PY - 1999/11/18

Y1 - 1999/11/18

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0033581919&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033581919&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1203084

DO - 10.1038/sj.onc.1203084

M3 - Article

C2 - 10597280

AN - SCOPUS:0033581919

VL - 18

SP - 6725

EP - 6732

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 48

ER -