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Submitted on May 23, 2003
Enabling Technologies/Genomics & Bioinformatics, Schering AG, Berlin 13342
Corresponding Author: anette.sommer{at}schering.de
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 (FaslodexTM, 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 2D-gels. 38 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 those are the protease cathepsin D, the GTPases Rab11a and MxA, and the secreted protein hAG-2. For nine proteins the corresponding mRNA was not found to be differentially expressed and for ten 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 to the antiestrogen-sensitive state.
Revised on September 21, 2003
Accepted on October 13, 2003
Comparison of proteomic and genomic analyses of the human breast cancer cell line T47D and the antiestrogen-resistant derivative T47D-r
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