Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth

Chun-Hong Zhu; Frederick E Domann

doi:10.1023/A:1013378113916

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Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth

Journal article

Peer reviewed

Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth

Chun-Hong Zhu and Frederick E Domann

Breast cancer research and treatment, Vol.71(1), pp.47-57

01/2002

DOI: 10.1023/A:1013378113916

PMID: 11859873

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Abstract

ErbB-3 (HER3) is a member of the epidermal growth factor receptor family. Increasing evidence suggests that elevated expression of ErbB-3 is important for malignancy. In this study, we found that elevated levels of ErbB-3 expression did not occur in the absence of AP-2gamma in a panel of human mammary epithelial and fibroblasts cell lines. In contrast, there was no association between the expression of AP-2alpha or AP-2beta and the level of ErbB-3, or between AP-2alpha and AP-2gamma double positivity and ErbB-3 expression. In co-transfection experiments, exogenous expression of AP-2gamma robustly activated ErbB-3 promoter activity. Moreover, expression of a dominant negative AP-2 protein, AP-2delta (deleted residues 31-117), not only repressed the ErbB-3 promoter activity but also suppressed endogenous ErbB-3 transcription in the ErbB-3 overexpressing cell line MRC-5VA. Overexpression of AP-2A resulted in a decreased proliferation rate and inhibitin of colony formation. Taken together, these data strongly support a role for the AP-2 gene family, in particular, AP-2gamma, in the control of ErbB-3 expression. Interference with the function of transcription factor AP-2 might provide a potential strategy for modulation of the malignant phenotype.

DNA-Binding Proteins - pharmacology

Breast - cytology

Fibroblasts - physiology

Genes, erbB

Humans

Gene Expression Regulation, Neoplastic

Lung - cytology

Transcription Factor AP-2

Breast Neoplasms - physiopathology

Receptor, ErbB-3 - biosynthesis

Phenotype

Breast Neoplasms - genetics

Cell Transformation, Neoplastic

Transcription Factors - pharmacology

Cell Division

Female

Breast - pathology

Details

Title: Subtitle: Dominant negative interference of transcription factor AP-2 causes inhibition of ErbB-3 expression and suppresses malignant cell growth
Creators: Chun-Hong Zhu - Free Radical & Radiation Biology Program, Department of Radiation Oncology, and Holden Comprehensive Cancer Center, The University of Iowa, Iowa City 52242, USA
Frederick E Domann
Resource Type: Journal article
Publication Details: Breast cancer research and treatment, Vol.71(1), pp.47-57
Publisher: Netherlands
DOI: 10.1023/A:1013378113916
PMID: 11859873
ISSN: 0167-6806
eISSN: 1573-7217
Grant note: P01-CA-66081 / NCI NIH HHS CA-73612 / NCI NIH HHS
Language: English
Date published: 01/2002
Academic Unit: Pathology; Surgery; Radiation Oncology
Record Identifier: 9984046911902771

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