Proteomics of xenografted human breast cancer indicates novel targets related to tamoxifen resistance
| Autor: | Yassel Ramos, Lila Castellanos-Serra, Michael Becker, Iduna Fichtner, Maylin Diaz, Vladimir Besada |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Proteomics
medicine.medical_specialty Antineoplastic Agents Hormonal Molecular Sequence Data Transplantation Heterologous Mice Nude Breast Neoplasms Biology Biochemistry Mice Breast cancer Internal medicine medicine Biomarkers Tumor Tumor Cells Cultured Neoplasm Animals Cluster Analysis Humans Electrophoresis Gel Two-Dimensional Amino Acid Sequence skin and connective tissue diseases Molecular Biology Sequence Homology Amino Acid Cancer medicine.disease Transplantation Tamoxifen Mitochondrial respiratory chain Endocrinology Drug Resistance Neoplasm Spectrometry Mass Matrix-Assisted Laser Desorption-Ionization Cancer research Female Signal transduction medicine.drug |
| Zdroj: | Proteomics. 6(3) |
| ISSN: | 1615-9853 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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