title: MHC-class-I expression in human breast cancer correlates with nuclear localization of the 90 kDa heat-shock-protein.
abstract: Breast cancer cells frequently exhibit a reduction in expression of major-histocompatibility-complex (MHC) class I proteins which blocks cytotoxic T-lymphocyte (CTL) mediated apoptosis. Recent studies indicate that the 90 kD heat-shock-protein (HSP90) plays a major role in the transfer of antigenic peptides to the MHC class I complex. HSP90 is a molecular chaperone which is involved in signal transduction and regulation of apoptosis. Since HSP90 is described to be elevated in breast cancer, its relationship with MHC class I expression was investigated. Using immunohistochemistry we analyzed the expression and localization of HSP90 and MHC class I in 17 human breast tumors. Positive correlation (p < 0.025) between strong nuclear staining for HSP90 and high MHC class I expression was observed. In tumors with reduced MHC class I expression, no nuclear localization of HSP90 was detectable. These findings lead to the hypothesis that tumor cells with high MHC class I expression and susceptibility to CTL action may escape apoptosis by a mechanism which involves increased nuclear HSP90.
authors.affiliation: Department of Surgery, University of Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Gebhard
authors.forename: G
authors.initials: G
authors.lastname: Schütz
authors.forename: R C
authors.initials: RC
authors.lastname: Ecker
authors.forename: G E
authors.initials: GE
authors.lastname: Steiner
authors.forename: M
authors.initials: M
authors.lastname: Rudas
authors.forename: M
authors.initials: M
authors.lastname: Gnant
authors.forename: R
authors.initials: R
authors.lastname: Oehler
mesh_terms: D001943:Breast Neoplasms / Q000276:immunology*; D002467:Cell Nucleus / Q000378:metabolism*; D015536:Down-Regulation; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism
chemical_list: D018841:HSP90 Heat-Shock Proteins; D015395:Histocompatibility Antigens Class I; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone