Dataset Information

Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.

ABSTRACT: 2C4 (Pertuzumab, Omnitarg) is a monoclonal antibody targeting p185(her2/neu), which is overexpressed in 30% of invasive breast cancer. 2C4 is currently in phase II clinical trials for several types of cancers. This antibody has been reported to disrupt the association between p185(her2/neu) and ErbB3. In our studies of epidermal growth factor receptor (EGFR)-p185(her2/neu) heterodimerization, we noted that 2C4 formed associations with the EGFR-p185(her2/neu) receptor complex. Our data argue against 2C4 as a universal heterodimerization blocker for p185(her2/neu), but indicate that cocktails of monoclonal antibodies binding distinct interaction surfaces of p185(her2/neu) will emerge as the most potent targeted therapy.

SUBMITTER: Cai Z

PROVIDER: S-EPMC2819401 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature

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Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.

Cai Z Z Zhang G G Zhou Z Z Bembas K K Drebin J A JA Greene M I MI Zhang H H

Oncogene 20080211 27

2C4 (Pertuzumab, Omnitarg) is a monoclonal antibody targeting p185(her2/neu), which is overexpressed in 30% of invasive breast cancer. 2C4 is currently in phase II clinical trials for several types of cancers. This antibody has been reported to disrupt the association between p185(her2/neu) and ErbB3. In our studies of epidermal growth factor receptor (EGFR)-p185(her2/neu) heterodimerization, we noted that 2C4 formed associations with the EGFR-p185(her2/neu) receptor complex. Our data argue agai ...[more]

PMID: 18264138

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Project description:Overexpression of the oncogene HER2/neu (c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/neu-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/neu-positive and three HER2/neu-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/neu overexpressers. In HER2/neu overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/neu protein levels. In contrast, in HER2/neu overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than up-regulated (N = 19, 0.4%). Many of the differentially expressed genes have previously not been known to play a role in human neoplasia, and some of them may represent novel tumor suppressor or oncogenes. No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/neu protein levels. These included transforming acidic coiled-coil containing protein 1, glycogen phosphorylase BB, complement 1q and one EST. The differential expression of select genes was confirmed by Northern blotting (trefoil factor 3) or by immunocytochemistry (glycogen phosphorylase BB, vimentin, KAI1). In an extended validation study, 18 of 41 ER-negative, but none of 46 ER-positive, breast carcinomas were found to express vimentin, and all but one of the vimentin-positive tumors were confined to the HER2/neu-negative subgroup (P = 0.0019). Our findings support an important role of the mammary stroma in determining the clinical breast cancer phenotype.

Dataset Information

Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.

Publications

Differential binding patterns of monoclonal antibody 2C4 to the ErbB3-p185her2/neu and the EGFR-p185her2/neu complexes.

Similar Datasets

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