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

Background: 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. Method: Immunohistochemistry for Bag-1...

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Bibliographic Details
Published in:British journal of cancer 2011-04, Vol.104 (9), p.1459-1471
Main Authors: Wood, J, Pring, M, Eveson, J W, Price, N, Proby, C M, Hague, A
Format: Article
Language:English
Subjects:
631/67/1059/2326
631/67/1059/99
692/420/2489/68
692/699/67/1813/1352
Antimetabolites, Antineoplastic - pharmacology
Apoptosis
Apoptosis - drug effects
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Breast cancer
Cancer Research
Cancer therapies
Carcinoma, Squamous Cell - drug therapy
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Line, Tumor
Chemotherapy
DNA-Binding Proteins - genetics
DNA-Binding Proteins - metabolism
Drug Resistance
Drug Resistance, Neoplasm - drug effects
Epidemiology
Fluorouracil - pharmacology
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Growth factors
Heat shock proteins
HSP70 Heat-Shock Proteins - metabolism
Humans
Immunohistochemistry
Keratinocytes - metabolism
Localization
Medical prognosis
Medical research
Melanoma
Molecular Diagnostics
Molecular Medicine
Mutation
Oncology
RNA, Small Interfering
Skin - metabolism
Skin cancer
Skin Neoplasms - drug therapy
Skin Neoplasms - metabolism
Skin Neoplasms - pathology
Transcription Factors - genetics
Transcription Factors - metabolism
Tumors
Up-Regulation
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Summary:Background: 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. Method: 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. Results: 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
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.111