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Proteomics of xenografted human breast cancer indicates novel targets related to tamoxifen resistance

Item Type:Article
Title:Proteomics of xenografted human breast cancer indicates novel targets related to tamoxifen resistance
Creators Name:Besada, V. and Diaz, M. and Becker, M. and Ramos, Y. and Castellanos-Serra, L. and Fichtner, I.
Abstract:Tamoxifen is the most frequently used drug for hormone therapy of breast cancer patients, even though a high percentage of women are (or become) refractory to this treatment. The proteins involved in tamoxifen resistance of breast tumor cells as well as the mechanisms by which they interact, are still unknown. Some years ago, we established the xenograft breast tumor 3366, sensitive to tamoxifen and the 3366/TAM, resistant to tamoxifen, derived after two years of in vivo passages of the parental 3366 under tamoxifen treatment. Here, we compare the protein expression levels of both xenografts. 2-DE of proteins from total cell extracts showed very high reproducibility among tumors from each group (tamoxifen sensitive and tamoxifen resistant). The heuristic clustering analysis of these gels pooled them correctly in both groups. Twelve proteins were found up-regulated in the tamoxifen-resistant line, while nine were down-regulated. The proteins differentially expressed were identified by MS and sequence database analysis. Biological functions of these proteins are related to cell-cell adhesion and interaction, signal transduction, DNA and protein synthesis machinery, mitochondrial respiratory chain, oxidative stress processes and apoptosis. Three of the identified proteins (ALG-2 interacting protein and two GDP-dissociation inhibitors) could be directly involved in the resistance phenomenon.
Keywords:Breast, Cancer, Resistance, Tamoxifen, Xenograft, Animals, Mice
Page Range:1038-1048
Date:February 2006
Official Publication:https://doi.org/10.1002/pmic.200500151
PubMed:View item in PubMed

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