Gebhard B, Schütz G, Ecker R C, Steiner G E, Rudas M, Gnant M, Oehler R
Department of Surgery, University of Vienna, Austria.
Anticancer Res. 1999 Nov-Dec;19(6B):5293-7.
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.
乳腺癌细胞常常表现出主要组织相容性复合体（MHC）I类蛋白表达降低，这会阻断细胞毒性T淋巴细胞（CTL）介导的细胞凋亡。最近的研究表明，90kD热休克蛋白（HSP90）在将抗原肽转运至MHC I类复合体过程中起主要作用。HSP90是一种分子伴侣，参与信号转导和细胞凋亡调控。由于HSP90在乳腺癌中表达升高，因此对其与MHC I类表达的关系进行了研究。我们采用免疫组织化学方法分析了17例人乳腺肿瘤中HSP90和MHC I类的表达及定位。观察到HSP90强核染色与高MHC I类表达之间呈正相关（p<0.025）。在MHC I类表达降低的肿瘤中，未检测到HSP90的核定位。这些发现提示，具有高MHC I类表达且对CTL作用敏感的肿瘤细胞可能通过一种涉及核内HSP90增加的机制逃避细胞凋亡。
