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Upregulated HSP27 in human breast cancer cells reduces Herceptin susceptibility by increasing Her2 protein stability.
- Source :
-
BMC cancer [BMC Cancer] 2008 Oct 04; Vol. 8, pp. 286. Date of Electronic Publication: 2008 Oct 04. - Publication Year :
- 2008
-
Abstract
- Background: Elucidating the molecular mechanisms by which tumors become resistant to Herceptin is critical for the treatment of Her2-overexpressed metastatic breast cancer.<br />Methods: To further understand Herceptin resistance mechanisms at the molecular level, we used comparative proteome approaches to analyze two human breast cancer cell lines; Her2-positive SK-BR-3 cells and its Herceptin-resistant SK-BR-3 (SK-BR-3 HR) cells.<br />Results: Heat-shock protein 27 (HSP27) expression was shown to be upregulated in SK-BR-3 HR cells. Suppression of HSP27 by specific siRNA transfection increased the susceptibility of SK-BR-3 HR cells to Herceptin. In the presence of Herceptin, Her2 was downregulated in both cell lines. However, Her2 expression was reduced by a greater amount in SK-BR-3 parent cells than in SK-BR-3 HR cells. Interestingly, co-immunoprecipitation analysis showed that HSP27 can bind to Her2. In the absence of Herceptin, HSP27 expression is suppressed and Her2 expression is reduced, indicating that downregulation of Her2 by Herceptin can be obstructed by the formation of a Her2-HSP27 complex.<br />Conclusion: Our present study demonstrates that upregulated HSP27 in human breast cancer cells can reduce Herceptin susceptibility by increasing Her2 protein stability.
- Subjects :
- Antibodies, Monoclonal, Humanized
Antineoplastic Agents pharmacology
Breast Neoplasms genetics
Breast Neoplasms pathology
Cell Line, Tumor
Drug Resistance, Neoplasm
Enzyme Stability
HSP27 Heat-Shock Proteins
Heat-Shock Proteins genetics
Humans
Molecular Chaperones
Neoplasm Metastasis
Neoplasm Proteins genetics
Trastuzumab
Up-Regulation
Antibodies, Monoclonal pharmacology
Breast Neoplasms drug therapy
Breast Neoplasms metabolism
Heat-Shock Proteins biosynthesis
Neoplasm Proteins biosynthesis
Receptor, ErbB-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1471-2407
- Volume :
- 8
- Database :
- MEDLINE
- Journal :
- BMC cancer
- Publication Type :
- Academic Journal
- Accession number :
- 18834540
- Full Text :
- https://doi.org/10.1186/1471-2407-8-286