Characterization of proteins associated with heat shock protein hsp27 in the squamous cell carcinoma cell line A431.

Department of Applied and Experimental Oncology, Institute of Tumorbiology/Cancer Research, Vienna, Austria.
Cell Biology International (Impact Factor: 1.64). 02/2002; 26(1):109-16. DOI: 10.1006/cbir.2001.0822
Source: PubMed

ABSTRACT Heat shock protein hsp27 is a molecular chaperone and identification of hsp27-binding proteins might help to elucidate its functional role in keratinocyte biology. In the present investigation we used a human epidermal cell carcinoma cell line (A431) transfected with hsp27 (A431/16) to study interference between hsp27 protein and other proteins. Immunoprecipitation experiments with anti-hsp27 antibody revealed a multicomponent complex when analysed by silver staining. By immunoblotting analysis we could demonstrate that hsp27 associates with actin, the mutant form of p53, hsp70 and hsp90. Immunofluorescence analysis showed a co-localization between hsp27 and p53, hsp70 and hsp90. To control for the specificity of the observed interactions, immuno-precipitations with antibodies to actin, p53, hsp70 and hsp90 respectively, were performed. All of the tested proteins demonstrated a coimmunoprecipitation with hsp27. We conclude that hsp27, like the other heat shock proteins, is part of a complex system of molecular chaperones in epidermal keratinocytes.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Heat shock proteins are molecular chaperones that may be constitutively present in cells protecting them from various stresses, such as extreme temperature, anoxia or chemical agents. Cervical cancer is the second most prevalent malignancy of women. In this study, we analyzed the expression of Hsp27 by immunohistochemistry in cervical intraepithelial lesions of Brazilian women, along with samples from non neoplasic lesions (NN). Cervical intraepithelial neoplasia I (CIN I), II (CIN II) and III (CIN III)/in situ carcinoma and squamous cell carcinoma (SCC) were included. Immunostaining was observed in 30 (100%) samples of NN, 46 (92%) in CIN I, 50 (100%) in CIN II, 52 (98.11%) in CIN III/CIS, and 46 (98.11%) in SCC. In group NN Hsp27 immunostaining was heterogeneous, more intense in basal and parabasal layers of the epithelium and less or absent in the intermediate and superficial layer. The majority of the samples of CIS and SCC presented strong staining in allepithelial layers. Metaplasic cells, when present, were strongly stained. In this study, Hsp27 protein was found to be commonly expressed in cervical epithelial cells.
    Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(9):5007-10. · 1.50 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The small heat shock protein, Hsp27, is elevated in a significant proportion of breast cancers. Over-expression of Hsp27 in breast cancer cells increases anchorage-independent growth, invasiveness and resistance to chemotherapeutic drugs and is associated with poor prognosis and shorter disease free survival in a proportion of cancer patients. Hsp27 acts in a complex manner to elicit diverse effects e.g. increasing survival in response to many stresses by acting either as a molecular chaperone, by association with components of the apoptotic machinery and/or by increasing cellular glutathione to regulate the redox state of the cells. Hsp27 also regulates cytoskeleton organization and stability. Therefore, factors that increase the expression and/or alter the functions of Hsp27 in breast cancer cells can affect disease progression and outcome following treatment. Although Hsp27 expression can be mediated via the classical Heat Shock response following stress, its elevation in breast cancer cells is associated with independent positive regulators which include the estrogen receptor (ER) and transcription factors such as Brn-3b and Sp1. HET/SAF-B negatively regulates Hsp27 in these cells. The effects of Hsp27 are also regulated post-translationally by phosphorylation at specific residues, which alter the oligomerization state of the protein and thus its effects in the cells. The expression, effects and mechanisms by which Hsp27 acts in breast cancer cells are described in this chapter
    09/2007: pages 93-130;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Heat shock protein 27 (Hsp27) is a chaperone protein and its expression is increased in response to various stress stimuli including anti-cancer chemotherapy, which allows the cells to survive and causes drug resistance. We previously identified lead compounds that bound to Hsp27 and tubulin via proteomic approaches. Systematic ligand based optimization in the current study significantly increased the cell growth inhibition and apoptosis inducing activities of the compounds. Compared to the lead compounds, one of the new derivatives exhibited much better potency to inhibit tubulin polymerization, but a decreased activity to inhibit Hsp27 chaperone function, suggesting that the structural modification dissected the dual targeting effects of the compound. The most potent compounds 20 and 22 exhibited strong cell proliferation inhibitory activities at subnanomolar concentration against 60 human cancer cell lines conducted by Developmental Therapeutic Program at the National Cancer Institute and represented promising candidates for anti-cancer drug development.
    Journal of Medicinal Chemistry 06/2013; · 5.61 Impact Factor


Available from