Mahvi D M, Carper S W, Storm F K, Teal S R, Sondel P M
Department of Surgery, University of Wisconsin School of Medicine, Madison 53792.
Cancer Immunol Immunother. 1993 Aug;37(3):181-6. doi: 10.1007/BF01525433.
Overexpression of the heat-shock protein hsp27 protein in primary breast cancers has been associated with early relapse in women with breast cancer. This study was designed to determine the role of the hsp27 protein in lymphocyte recognition of estrogen-receptor(ER)-positive breast cancer cells and to assess the effect of hsp27 expression on lymphocyte-mediated lysis. The hsp27 cDNA was inserted into the pHbAPr-1-neo plasmid expression vector and driven by the constitutive actin promoter. The ER-positive MCF-7 human breast cancer cell line was then transfected with this vector and the resulting clonal cell lines were confirmed to overexpress hsp27. hsp27-transfected clonal cell lines stimulated the proliferation of fresh peripheral blood lymphocytes (PBL) significantly better than control cells transfected with the expression vector alone. When clonal gamma delta T cell lines were utilized as effectors, hsp27-transfected cell lines were significantly better targets for lysis than a control-transfected MCF-7 cell line. In contrast, hsp27-transfected cell lines had no increase in susceptibility to lymphokine-activated-killer- or natural-killer-mediated lysis. These results suggest that overexpression of the hsp27 protein in ER-positive MCF-7 cells stimulated the proliferation of fresh PBL and the lysis of MCF-7 cells by gamma delta T cell clones.
原发性乳腺癌中热休克蛋白hsp27的过表达与乳腺癌女性的早期复发有关。本研究旨在确定hsp27蛋白在淋巴细胞识别雌激素受体(ER)阳性乳腺癌细胞中的作用,并评估hsp27表达对淋巴细胞介导的细胞裂解的影响。将hsp27 cDNA插入pHbAPr-1-neo质粒表达载体,并由组成型肌动蛋白启动子驱动。然后用该载体转染ER阳性的MCF-7人乳腺癌细胞系,所得克隆细胞系经证实过表达hsp27。hsp27转染的克隆细胞系比单独用表达载体转染的对照细胞显著更好地刺激新鲜外周血淋巴细胞(PBL)的增殖。当克隆的γδT细胞系用作效应细胞时,hsp27转染的细胞系作为细胞裂解的靶细胞比对照转染的MCF-7细胞系显著更好。相反,hsp27转染的细胞系对淋巴因子激活的杀伤细胞或自然杀伤细胞介导的细胞裂解的敏感性没有增加。这些结果表明,ER阳性MCF-7细胞中hsp27蛋白的过表达刺激了新鲜PBL的增殖以及γδT细胞克隆对MCF-7细胞的裂解。