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Derlin-1 is overexpressed in human breast carcinoma and protects cancer cells from endoplasmic reticulum stress-induced apoptosis
INTRODUCTION: Aberrant microenvironment and endoplasmic reticulum (ER) stress are associated with solid-tumor progression. Stress proteins, like heat shock proteins and glucose-regulated proteins, are frequently overexpressed in human tumors. It has been reported that derlin-1 is involved in ER stre...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2008
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2374959/ https://www.ncbi.nlm.nih.gov/pubmed/18205950 http://dx.doi.org/10.1186/bcr1849 |
Sumario: | INTRODUCTION: Aberrant microenvironment and endoplasmic reticulum (ER) stress are associated with solid-tumor progression. Stress proteins, like heat shock proteins and glucose-regulated proteins, are frequently overexpressed in human tumors. It has been reported that derlin-1 is involved in ER stress response. In vitro studies have demonstrated that derlin-1 participates in the retrotranslocation of misfolded proteins from ER into the cytosol. Because the roles of derlin-1 in human cancer have not yet been characterized, we investigated the expression of derlin-1 in human breast carcinoma and whether it protected cancer cells against ER stress-induced apoptosis. METHODS: Surgical specimens of human breast cancer and/or paired normal tissues from the same patients were collected for immunohistochemical and/or Western blot analysis with anti-human derlin-1 antibody. The expression of derlin-1 in human breast cancer cell lines was detected by reverse transcription-polymerase chain reaction or Western blot. A synthetic small interfering RNA against derlin-1 was introduced into breast cancer cells to inhibit derlin-1 expression. The effects of derlin-1 knockdown on ER stress-induced apoptosis were determined by flow cytometry analysis. RESULTS: These analyses demonstrated that 66.7% of the breast carcinoma tissues expressed derlin-1, whereas derlin-1 was rarely expressed in normal mammary glands. The expression of derlin-1 in human breast carcinoma correlated with tumor grade and axillary lymph node metastasis. On examining the expression of derlin-1 in human breast cancer cell lines, we found that derlin-1 expression was enhanced by ER stress-inducing agents. Derlin-1 knockdown sensitized breast cancer cells to ER stress-induced apoptosis. CONCLUSION: The observed derlin-1 overexpression in breast cancer, together with its function in relieving ER stress-induced apoptosis, suggests that regulation of the ER stress response pathway may be critical in the development and progression of breast cancer. |
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