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Comparison of proteomic and genomic analyses of the human breast cancer cell line T47D and the antiestrogen-resistant derivative T47D-r

Item Type:Article
Title:Comparison of proteomic and genomic analyses of the human breast cancer cell line T47D and the antiestrogen-resistant derivative T47D-r
Creators Name:Huber, M. and Bahr, I. and Kraetzschmar, J.R. and Becker, A. and Mueller, E.C. and Donner, P. and Pohlenz, H.D. and Schneider, M.R. and Sommer, A.
Abstract:In search of novel mechanisms leading to the development of antiestrogen-resistance in human breast tumors, we analyzed differences in the gene and protein expression pattern of the human breast carcinoma cell line T47D and its derivative T47D-r, which is resistant toward the pure antiestrogen ZM 182780 (Faslodex trade mark, fulvestrant). Affymetrix DNA chip hybridizations on the commercially available HuGeneFL and Hu95A arrays were carried out in parallel to the proteomics analysis where the total cellular protein content of T47D or T47D-r was separated on two-dimensional gels. Thirty-eight proteins were found to be reproducibly up- or down-regulated more than 2-fold in T47D-r versus T47D in the proteomics analysis. Comparison with differential mRNA analysis revealed that 19 of these were up- or down-regulated in parallel with the corresponding mRNA molecules, among which are the protease cathepsin D, the GTPases Rab11a and MxA, and the secreted protein hAG-2. For 11 proteins, the corresponding mRNA was not found to be differentially expressed, and for eight proteins an inverse regulation was found at the mRNA level. In summary, mRNA expression data, when combined with proteomic information, provide a more detailed picture of how breast cancer cells are altered in their antiestrogen-resistant compared with the antiestrogen-sensitive state.
Keywords:Breast Neoplasms, Tumor Cell Line, Neoplasm Drug Resistance, Estradiol, Estrogen Antagonists, Estrogen Receptor Modulators, Gene Expression Profiling, Neoplastic Gene Expression Regulation, Genome, Oligonucleotide Array Sequence Analysis, Proteome, Proteomics, Messenger RNA
Source:Molecular and Cellular Proteomics
ISSN:1535-9476
Publisher:American Society for Biochemistry and Molecular Biology (U.S.A.)
Volume:3
Number:1
Page Range:43-55
Date:January 2004
Official Publication:https://doi.org/10.1074/mcp.M300047-MCP200
PubMed:View item in PubMed

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