Co-overexpression of Bag-1 and heat shock protein 70 in human epidermal squamous cell carcinoma: Bag-1-mediated resistance to 5-fluorouracil-induced apoptosis
Copyright policy )Co-overexpression of Bag-1 and heat shock protein 70 in human epidermal squamous cell carcinoma: Bag-1-mediated resistance to 5-fluorouracil-induced apoptosis
The aim was to determine whether Bcl-2-associated athanogene-1 (Bag-1) and/or its binding protein heat shock protein-70 (Hsp70) exhibit deregulated expression in epidermal squamous cell carcinoma (SCC) and whether Bag-1 confers apoptosis resistance.Immunohistochemistry for Bag-1 and Hsp70 was performed on 60 epidermal SCC and 10 normal skin samples. The epidermal SCC cell line SCC-13 was treated with 5-fluorouracil (5-FU) after Bag-1 knockdown to determine whether high Bag-1 levels contribute to growth and/or apoptosis resistance.Normal epithelium expressed primarily nuclear Bag-1. Most tumours showed reduced nuclear Bag-1 staining, but a subset exhibited strong Bag-1 staining, with cytoplasmic Bag-1 staining intensity correlating with cytoplasmic Hsp70 staining intensity (r(s)=0.462; P<0.001) and less differentiation (P<0.001). Bag-1 knockdown resulted in markedly reduced SCC-13 cell yield, increased spontaneous apoptosis and enhanced sensitivity to 5-FU-induced apoptosis. Apoptosis induced by 5-FU in the Bag-1-knockdown cells was significantly greater than the additive apoptotic effect of 5-FU or Bag-1 knockdown alone.Overexpression of Bag-1 and Hsp70 in poorly differentiated SCC may confer both enhanced tumour cell growth and apoptosis resistance. Bag-1 may contribute to the resistance of more advanced epidermal SCC to chemotherapy.
- University of Bristol United Kingdom
- University of Dundee United Kingdom
EXPRESSION, Keratinocytes, skin, Antimetabolites, Antineoplastic, Skin Neoplasms, Blotting, Western, BCL-2, 610, LINES, Apoptosis, PROTEIN BAG-1, TUMOR, Cell Line, Tumor, Humans, 5-fluorouracil, HSP70 Heat-Shock Proteins, RNA, Small Interfering, Molecular Diagnostics, Bag-1, Skin, P53, SKIN-CANCER, apoptosis, heat shock protein-70, Immunohistochemistry, ALTERNATIVE TRANSLATION INITIATION, Up-Regulation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Gene Knockdown Techniques, immunohistochemistry, COLORECTAL ADENOMA, SURVIVAL, Carcinoma, Squamous Cell, Fluorouracil, Transcription Factors
EXPRESSION, Keratinocytes, skin, Antimetabolites, Antineoplastic, Skin Neoplasms, Blotting, Western, BCL-2, 610, LINES, Apoptosis, PROTEIN BAG-1, TUMOR, Cell Line, Tumor, Humans, 5-fluorouracil, HSP70 Heat-Shock Proteins, RNA, Small Interfering, Molecular Diagnostics, Bag-1, Skin, P53, SKIN-CANCER, apoptosis, heat shock protein-70, Immunohistochemistry, ALTERNATIVE TRANSLATION INITIATION, Up-Regulation, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Drug Resistance, Neoplasm, Gene Knockdown Techniques, immunohistochemistry, COLORECTAL ADENOMA, SURVIVAL, Carcinoma, Squamous Cell, Fluorouracil, Transcription Factors
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