Vargas-Roig L M, Fanelli M A, López L A, Gago F E, Tello O, Aznar J C, Ciocca D R
Laboratory of Reproduction and Lactation, Regional Center for Scientific and Technological Research, Mendoza, Argentina.
Cancer Detect Prev. 1997;21(5):441-51.
Human breast cancers may overexpress certain heat shock protein (hsp) family members, proteins which are involved with cell proliferation and differentiation as well as with disease prognosis and drug resistance. Here, we have studied the relationship between the expression of two hsps (hsp27 and hsp70) and the proliferative activity of tumor cells in 40 biopsies from breast cancer patients. Twenty of these tumors were selected for a detailed colocalization study. Immunocytochemistry was done using specific antibodies against hsp27 and hsp70. Cell proliferation was studied analyzing the expression of proliferating cell nuclear antigen (PCNA) (late G1, S, and G2 phases of the cell cycle) and the number of silver-staining nucleolar organizer regions (AgNORs) (G1 phase). The colocalization study revealed a statistically significant inverse correlation between hsp27 expression and cell proliferation in 16/19 (84%) of the cases evaluated by PCNA immunostaining, and in 11/16 (69%) of the cases evaluated by AgNORs. In contrast, a statistically significant positive correlation between hsp70 expression and elevated cell proliferation was seen in almost 85% of the cases evaluated by PCNA staining, and in almost 50% of the cases evaluated by AgNORs. Moreover, in 22% (9/40) of the breast cancer samples examined, hsp70 was clearly associated with the mitotic spindle. A Western blot analysis revealed that hsp70 was coprecipitated with taxol-polymerized tubulin. The association of hsp70 with the mitotic spindle was not clearly noted in lung carcinoma samples (N = 20) or in normal cells displaying elevated mitotic activity. These studies thus demonstrate that in a significant percentage of clinical breast cancers hsp27 overexpression is inversely correlated with cell proliferation, while hsp70 is clearly associated with the mitotic spindle and cell proliferation. These results add evidence to the concept that in human breast cancers hsp27 may be involved in cell growth arrest and increased differentiation while, in contrast, hsp70 may be involved in cell proliferation; further studies will be necessary to elucidate these possible cause-and-effect relationships.
人类乳腺癌可能会过度表达某些热休克蛋白（hsp）家族成员，这些蛋白与细胞增殖、分化以及疾病预后和耐药性有关。在此，我们研究了40例乳腺癌患者活检样本中两种热休克蛋白（hsp27和hsp70）的表达与肿瘤细胞增殖活性之间的关系。其中20个肿瘤样本被选用于详细的共定位研究。使用针对hsp27和hsp70的特异性抗体进行免疫细胞化学检测。通过分析增殖细胞核抗原（PCNA）（细胞周期的G1晚期、S期和G2期）的表达以及银染核仁组织区（AgNORs）的数量（G1期）来研究细胞增殖。共定位研究显示，在通过PCNA免疫染色评估的16/19（84%）病例中，以及在通过AgNORs评估的11/16（69%）病例中，hsp27表达与细胞增殖之间存在统计学上显著的负相关。相反，在通过PCNA染色评估的近85%病例中，以及在通过AgNORs评估的近50%病例中，hsp70表达与细胞增殖增加之间存在统计学上显著的正相关。此外，在检测的22%（9/40）乳腺癌样本中，hsp70与有丝分裂纺锤体明显相关。蛋白质印迹分析显示，hsp70与紫杉醇聚合的微管蛋白共沉淀。在肺癌样本（N = 20）或有丝分裂活性升高的正常细胞中，未明显观察到hsp70与有丝分裂纺锤体的关联。因此，这些研究表明，在相当比例的临床乳腺癌中，hsp27的过度表达与细胞增殖呈负相关，而hsp70与有丝分裂纺锤体和细胞增殖明显相关。这些结果为以下概念提供了证据：在人类乳腺癌中，hsp27可能参与细胞生长停滞和分化增加，而相反，hsp70可能参与细胞增殖；需要进一步研究来阐明这些可能的因果关系。
