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

J. Wood, M. Pring, J. W. Eveson, N. Price, C. M. Proby, A. Hague

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    10 Citations (Scopus)

    Abstract

    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<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.

    CONCLUSIONS: 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. British Journal of Cancer (2011) 104, 1459-1471. doi:10.1038/bjc.2011.111 www.bjcancer.com (C) 2011 Cancer Research UK

    Original languageEnglish
    Pages (from-to)1459-1471
    Number of pages13
    JournalBritish Journal of Cancer
    Volume104
    Issue number9
    DOIs
    Publication statusPublished - 26 Apr 2011

    Keywords

    • Bag-1
    • heat shock protein-70
    • skin
    • apoptosis
    • immunohistochemistry
    • 5-fluorouracil
    • ALTERNATIVE TRANSLATION INITIATION
    • PROTEIN BAG-1
    • SKIN-CANCER
    • COLORECTAL ADENOMA
    • EXPRESSION
    • LINES
    • P53
    • SURVIVAL
    • TUMOR
    • BCL-2

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