IMR Press / FBE / Volume 2 / Issue 2 / DOI: 10.2741/E119

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Characterization of a novel, trastuzumab resistant human breast cancer cell line
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1 Department of Biophysics and Cell Biology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
2 Department of Preventive Medicine, Faculty of Public Health, Medical and Health Science Center, University of Debrecen, Debrecen, Hungary
3 Public Health Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary
4 Division of Hematology/Oncology, Department of Medicine, University of California, San Francisco, USA
5 Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary

*Author to whom correspondence should be addressed.

Front. Biosci. (Elite Ed) 2010, 2(2), 627–640; https://doi.org/10.2741/E119
Published: 1 January 2010
Abstract

HER2-positive breast cancers represent a distinct phenotype and are intrinsically more aggressive than HER2-negative tumors. Although HER2-targeted therapies have been rationally developed, resistance to these treatments represents a process understood poorly. There are few experimental models that allow studying the molecular mechanism of resistance. Our aim was to characterize a trastuzumab resistant breast cancer cell line (B585) that was established from an invasive ductal carcinoma. B585 grows only in immunodeficient mice as a xenograft. CGH and FISH were used to define cytogenetic alterations, gene-expression analysis and immunohistochemistry were applied to detect RNA and protein expression. By array-CGH focused amplifications were identified for C-MYC, EGFR, ErbB2, CCND1 and TOP2-A oncogenes. ErbB2 was co-amplified with TOP2-A. mRNA overexpression was detected for the amplified genes. ErbB2 protein was overexpressed and showed heterogeneous distribution. In summary, molecular cytogenetic analysis and expression profiling of B585 revealed several new alterations. Based on the experiments performed in SCID mice and the genotypic/phenotypic characteristics, this new in vivo breast cancer xenograft is a valuable model to investigate molecular mechanism of trastuzumab resistance.

Keywords
Drug Resistance
Trastuzumab
Breast Tumor Xenograft
ErbB2/HER-2
array-CGH
Gene And Protein Expression
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