SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells

Yongjin Park, Soo Kyung Shon, Aeyung Kim, Keun Il Kim, Young Yang, Dae Ho Cho, Myeong Sok Lee, Jong Seok Lim

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Although NDRG2 inactivation has recently been found to have an important role in some tumorigenesis, its role in intracellular signal transduction pathways remains poorly defined. In the present study, we demonstrate that NDRG2 overexpression in malignant breast cancer cells specifically inhibits Akt phosphorylation and induces phosphorylation of p38 MAP kinase and SAPK/JNK. In addition, we investigated whether NDRG2 expression affects JAK/STAT- or mitogen-activated protein kinase-mediated signal activation. JAK2 or STAT3 activation in both resting and IGF-stimulating cells was remarkably inhibited by NDRG2 expression. Furthermore, NDRG2 has been found to highly up-regulate the expression level of SOCS1 mRNA and protein. We have found that NDRG2 was able to regulate cytokine signaling in breast cancer cells through the regulation of SOCS1 expression. Finally, inhibition of p38 MAPK activity blocked the induction of SOCS1 expression by NDRG2, resulting in the recovery of STAT3 phosphorylation level. Together, these data demonstrate that NDRG2 expression in breast cancer cells is able to inhibit STAT3 activation via SOCS1 induction in a p38 MAPK dependent manner, implicating NDRG2 as a growth inhibitory gene in signal transduction pathways of breast tumor cells.

Original languageEnglish
Pages (from-to)361-367
Number of pages7
JournalBiochemical and biophysical research communications
Volume363
Issue number2
DOIs
Publication statusPublished - 2007 Nov 16
Externally publishedYes

Fingerprint

Phosphorylation
p38 Mitogen-Activated Protein Kinases
Chemical activation
Cells
Breast Neoplasms
Signal transduction
Signal Transduction
Mitogen-Activated Protein Kinases
Tumors
Genes
Cytokines
Carcinogenesis
Recovery
Up-Regulation
Messenger RNA
Growth
Proteins

Keywords

  • Breast cancer
  • MAPK
  • NDRG2
  • SOCS
  • STAT

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells. / Park, Yongjin; Shon, Soo Kyung; Kim, Aeyung; Kim, Keun Il; Yang, Young; Cho, Dae Ho; Lee, Myeong Sok; Lim, Jong Seok.

In: Biochemical and biophysical research communications, Vol. 363, No. 2, 16.11.2007, p. 361-367.

Research output: Contribution to journalArticle

Park, Yongjin ; Shon, Soo Kyung ; Kim, Aeyung ; Kim, Keun Il ; Yang, Young ; Cho, Dae Ho ; Lee, Myeong Sok ; Lim, Jong Seok. / SOCS1 induced by NDRG2 expression negatively regulates STAT3 activation in breast cancer cells. In: Biochemical and biophysical research communications. 2007 ; Vol. 363, No. 2. pp. 361-367.
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