Vargas-Roig L M, Gago F E, Tello O, Aznar J C, Ciocca D R
Laboratory of Reproduction and Lactaction, Regional Center for Scientific and Technological Research, Mendoza, Argentina.
Int J Cancer. 1998 Oct 23;79(5):468-75. doi: 10.1002/(sici)1097-0215(19981023)79:5<468::aid-ijc4>3.0.co;2-z.
Heat shock proteins (Hsps) are induced in vitro by several cytotoxic drugs; in human breast cancer cells these proteins appear to be involved in anti-cancer drug resistance. The present report was designed to analyze whether chemotherapy affects in vivo the expression of Hsp27, Hsp70, Hsc70 and Hsp90 in breast cancer patients treated with induction chemotherapy and whether these proteins may be determinants of tumor resistance to drug administration. We have analyzed 35 biopsies from breast cancer patients treated with induction chemotherapy. Expression of the Hsps in the tumors was compared with (i) histological and clinical responses to chemotherapy, (ii) tumor cell proliferation measured by proliferating cell nuclear antigen (PCNA) immunostaining and nucleolar organizer regions (AgNORs) staining and (iii) the expression of estrogen and progesterone receptors. We also compared disease-free survival (DFS) and overall survival (OS) with the expression of the Hsps studied. After chemotherapy, nuclear Hsp27 and Hsp70 expression was increased and Hsp70 and Hsc70 cytoplasmic expression was decreased. A high nuclear proportion of Hsp70 in tumor cells (>10%) correlated significantly with drug resistance. We also observed that patients whose tumors expressed nuclear or a high cytoplasmic proportion (>66%) of Hsp27 had shorter DFS. The combination of Hsp27 and Hsp70 levels showed a strong correlation with DFS. Neither the cellular proliferation nor the levels of steroid receptors showed any significant difference before or after drug administration or during follow-up of patients. Our results suggest that Hsp27 and Hsp70 are involved in drug resistance in breast cancer patients treated with combination chemotherapies.
热休克蛋白（Hsps）在体外可被多种细胞毒性药物诱导产生；在人乳腺癌细胞中，这些蛋白似乎与抗癌药物耐药性有关。本报告旨在分析化疗对接受诱导化疗的乳腺癌患者体内Hsp27、Hsp70、Hsc70和Hsp90表达的影响，以及这些蛋白是否可能是肿瘤对药物治疗耐药性的决定因素。我们分析了35例接受诱导化疗的乳腺癌患者的活检样本。将肿瘤中热休克蛋白的表达与以下因素进行比较：（i）化疗的组织学和临床反应；（ii）通过增殖细胞核抗原（PCNA）免疫染色和核仁组织区（AgNORs）染色测量的肿瘤细胞增殖；（iii）雌激素和孕激素受体的表达。我们还将无病生存期（DFS）和总生存期（OS）与所研究的热休克蛋白的表达进行了比较。化疗后，核内Hsp27和Hsp70表达增加，而Hsp70和Hsc70的胞质表达减少。肿瘤细胞中Hsp70的高核比例（>10%）与耐药性显著相关。我们还观察到，肿瘤表达核内Hsp27或高胞质比例（>66%）的患者DFS较短。Hsp27和Hsp70水平的联合显示与DFS有很强的相关性。无论是细胞增殖还是类固醇受体水平，在给药前、给药后或患者随访期间均未显示出任何显著差异。我们的结果表明，Hsp27和Hsp70参与了接受联合化疗的乳腺癌患者的耐药过程。
