Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells

Yun Jung Park; Hansoo Lee; Jeong-Hyung Lee

doi:10.5483/bmbrep.2010.43.2.091

Macrophage inhibitory cytokine-1 transactivates ErbB family receptors via the activation of Src in SK-BR-3 human breast cancer cells

BMB Rep. 2010 Feb;43(2):91-6. doi: 10.5483/bmbrep.2010.43.2.091.

Authors

Yun Jung Park¹, Hansoo Lee, Jeong-Hyung Lee

Affiliation

¹ Departments of Biochemistry and College of Natural Sciences, Kangwon National University, Chuncheon 200-701, Korea.

PMID: 20193126
DOI: 10.5483/bmbrep.2010.43.2.091

Abstract

The function of macrophage inhibitory cytokine-1 (MIC-1) in cancer remains controversial, and its signaling pathways remain poorly understood. In this study, we demonstrate that MIC-1 induces the transactivation of EGFR, ErbB2, and ErbB3 through the activation of c-Src in SK-BR-3 breast cells. MIC-1 induced significant phosphorylation of EGFR at Tyr845, ErbB2 at Tyr877, and ErbB3 at Tyr1289 as well as Akt and p38, Erk1/2, and JNK mitogen-activated protein kinases (MAPKs). Treatment of SK-BR-3 cells with MIC-1 increased the phosphorylation level of Src at Tyr416, and induced invasiveness of those cells. Inhibition of c-Src activity resulted in the complete abolition of MIC-1-induced phosphorylation of the EGFR, ErbB2, and ErbB3, as well as invasiveness and matrix metalloproteinase (MMP)-9 expression in SK-BR-3 cells. Collectively, these results show that MIC-1 may participate in the malignant progression of certain cancer cells through the activation of c-Src, which in turn may transactivate ErbB-family receptors.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms / metabolism*
Cell Line, Tumor
ErbB Receptors / metabolism*
Female
Growth Differentiation Factor 15 / genetics
Growth Differentiation Factor 15 / isolation & purification
Growth Differentiation Factor 15 / pharmacology*
Humans
JNK Mitogen-Activated Protein Kinases / metabolism
Matrix Metalloproteinase 9 / metabolism
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins pp60(c-src) / metabolism*
Recombinant Proteins / genetics
Recombinant Proteins / isolation & purification
Recombinant Proteins / pharmacology
p38 Mitogen-Activated Protein Kinases / metabolism

Substances

Growth Differentiation Factor 15
Recombinant Proteins
ErbB Receptors
Proto-Oncogene Proteins pp60(c-src)
Proto-Oncogene Proteins c-akt
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
Matrix Metalloproteinase 9