Langdon S P, Rabiasz G J, Hirst G L, King R J, Hawkins R A, Smyth J F, Miller W R
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Edinburgh EH4 2XU, United Kingdom.
Clin Cancer Res. 1995 Dec;1(12):1603-9.
The relationship of the heat shock protein HSP27 in ovarian cancer to several biological and clinical parameters was investigated in a series of primary tumors and cell lines. Analysis of 72 primary tumors (54 malignant, 5 borderline, and 13 benign neoplasms) indicated that malignant tumors expressed higher HSP27 concentrations than benign tumors (median values, 0.56 versus 0.25 ng/microgram cytosolic protein; P = 0.032). Tumors from patients with advanced stage (stages II, III, or IV) disease contained significantly higher HSP27 concentrations than tumors from stage I patients (P = 0.018), and an HSP27 content >2.0 ng/microgram cytosolic protein was associated with reduced survival (P = 0.03). Tumors that had demonstrated progressive growth after chemotherapy had a significantly higher HSP27 content than tumors that were static or responsive (P = 0.022). These data indicate that HSP27 is associated with more aggressive malignant ovarian disease and with inherent resistance to chemotherapy. Concentrations of HSP27 were also correlated with indicators of estrogen sensitivity. Therefore, the HSP27 concentration correlated with the estrogen receptor (all tumors, P = 0.0014; malignant tumors only, P = 0.047) but not with the progesterone receptor concentration. Analysis of ovarian cancer cell lines in vitro and in vivo indicated that the HSP27 content was higher in cell lines that were estrogen receptor rich and whose growth was modulated by estrogen as compared with those that were not. Additionally, two estrogen receptor-rich ovarian carcinoma lines demonstrated a small but significant decrease in HSP27 levels in response to 17beta-estradiol in culture. These results suggest that HSP27 may help identify tumors responsive to estrogens.
在一系列原发性肿瘤和细胞系中研究了热休克蛋白HSP27在卵巢癌中与多种生物学和临床参数的关系。对72例原发性肿瘤（54例恶性、5例交界性和13例良性肿瘤）的分析表明，恶性肿瘤表达的HSP27浓度高于良性肿瘤（中位值分别为0.56 ng/微克胞质蛋白和0.25 ng/微克胞质蛋白；P = 0.032）。晚期（II、III或IV期）疾病患者的肿瘤所含HSP27浓度显著高于I期患者的肿瘤（P = 0.018），且HSP27含量>2.0 ng/微克胞质蛋白与生存率降低相关（P = 0.03）。化疗后呈进行性生长的肿瘤的HSP27含量显著高于静止或有反应的肿瘤（P = 0.022）。这些数据表明，HSP27与侵袭性更强的恶性卵巢疾病以及对化疗的固有耐药性相关。HSP27的浓度也与雌激素敏感性指标相关。因此，HSP27浓度与雌激素受体相关（所有肿瘤，P = 0.0014；仅恶性肿瘤，P = 0.047），但与孕激素受体浓度无关。对卵巢癌细胞系的体外和体内分析表明，与雌激素受体缺乏且生长不受雌激素调节的细胞系相比，雌激素受体丰富且生长受雌激素调节的细胞系中HSP27含量更高。此外，两个雌激素受体丰富的卵巢癌细胞系在培养中对17β-雌二醇有反应，HSP27水平有小幅但显著的下降。这些结果表明，HSP27可能有助于识别对雌激素有反应的肿瘤。
