Induction or suppression of expression of cytochrome C oxidase subunit II by heregulin beta 1 in human mammary epithelial cells is dependent on the levels of ErbB2 expression

Yanbo Sun; Hong Lin; Yunfeng Zhu; Cuiling Ma; Jianping Ye; Jia Luo

doi:10.1002/jcp.10132

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Induction or suppression of expression of cytochrome C oxidase subunit II by heregulin beta 1 in human mammary epithelial cells is dependent on the levels of ErbB2 expression

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Induction or suppression of expression of cytochrome C oxidase subunit II by heregulin beta 1 in human mammary epithelial cells is dependent on the levels of ErbB2 expression

Yanbo Sun, Hong Lin, Yunfeng Zhu, Cuiling Ma, Jianping Ye and Jia Luo

Journal of cellular physiology, Vol.192(2), pp.225-233

08/2002

DOI: 10.1002/jcp.10132

PMID: 12115729

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Abstract

The ErbB family of receptor kinases is composed of four members: epidermal growth factor receptor (EGFR/ErbB1), ErbB2/neu, ErbB3, and ErbB4. Amplification of the ErbB2/neu is found in about 30% of breast cancer patients and is associated with a poor prognosis. Heregulin (HRG) activates the ErbB2 via induction of heterodimerization with ErbB3 and ErbB4 receptors. With suppression subtractive hybridization, we demonstrated that the expression of cytochrome c oxidase subunit II (COXII) is HRG-responsive. Two nontransformed human mammary epithelial cell lines, the HB2 and the HB2(ErbB2) (the HB2 engineered to overexpress ErbB2), displayed an opposite response to HRG-mediated regulation. HRG upregulated mRNA expression of COXII in the HB2 cells, but suppressed COXII expression in the HB2(ErbB2) cells. A human breast cancer cell line (T47D), which expresses ErbB2 at a level similar to that of the HB2 cells, also responded to HRG by increasing COXII mRNA levels. Therefore, HRG regulation of COXII expression depends on the levels of ErbB2 expression. Furthermore, the expression of COXII was inversely correlated to the levels of ErbB2, i.e., the cells overexpressing ErbB2 exhibited lower COXII levels. HRG-evoked signal transduction differed between the cells with normal ErbB expression and the cells overexpressing ErbB2. The activation of both ERK and PI3-K was essential for HRG regulation of COXII, i.e., blockage of either pathway eliminated HRG-mediated alteration. This is the first report demonstrating that the expression of mitochondria-encoded COXII is HRG-responsive. The levels of ErbB2 expression are decisive for the diverse biological activities of HRG.

Breast Neoplasms - metabolism

Electron Transport Complex IV - genetics

Electron Transport Complex IV - metabolism

Enzyme Activation

Gene Expression Regulation

Humans

Mitogen-Activated Protein Kinases - metabolism

Neuregulin-1 - physiology

Phosphatidylinositol 3-Kinases - metabolism

Plant Proteins - genetics

Plant Proteins - metabolism

Receptor, ErbB-2 - metabolism

Tumor Cells, Cultured

Details

Title: Subtitle: Induction or suppression of expression of cytochrome C oxidase subunit II by heregulin beta 1 in human mammary epithelial cells is dependent on the levels of ErbB2 expression
Creators: Yanbo Sun - West Virginia University
Hong Lin - West Virginia University
Yunfeng Zhu - West Virginia University
Cuiling Ma - West Virginia University
Jianping Ye - Louisiana State University
Jia Luo - West Virginia University
Resource Type: Journal article
Publication Details: Journal of cellular physiology, Vol.192(2), pp.225-233
DOI: 10.1002/jcp.10132
PMID: 12115729
ISSN: 0021-9541
eISSN: 1097-4652
Grant note: AA12968 / NIAAA NIH HHS CA90385 / NCI NIH HHS
Language: English
Date published: 08/2002
Academic Unit: Pathology
Record Identifier: 9984186494402771

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