Ciocca D R, Oesterreich S, Chamness G C, McGuire W L, Fuqua S A
Department of Medicine, University of Texas Health Science Center at San Antonio 78284-7884.
J Natl Cancer Inst. 1993 Oct 6;85(19):1558-70. doi: 10.1093/jnci/85.19.1558.
Heat shock and other environmental and pathophysiologic stresses stimulate synthesis of heat shock proteins (Hsps). These proteins enable the cell to survive and recover from stressful conditions by as yet uncompletely understood mechanisms. Hsp27 is an important small Hsp (molecular weight, 27,000) found in human cells--both cancer cells and normal cells. This protein, besides its putative role in thermotolerance, is of special clinical interest because of recent data suggesting it may also play a role in drug resistance. In adults, Hsp27 is found particularly in several cell types such as breast, uterus, cervix, placenta, skin, and platelets. Although low-molecular-weight (small) Hsps have been found to be involved in embryogenesis of Xenopus and Drosophila, they have not been detected in human fetal organs. Regulation of expression of the Hsp gene (also known as HSPB1) has been considered a paradigm of gene regulation and is actively being studied in both prokaryotes and eukaryotes. In prokaryotes, the major Hsp genes are transcriptionally regulated by positively and negatively acting transcription factors. In eukaryotes, the genes encoding Hsps contain a regulatory DNA motif (inverted repeats of the pentameric sequence nGAAn) known as the heat shock element. Hsp27 may function as a molecular chaperone and in signal transduction pathways of different cell regulators, and Hsp27 and other Hsps may be active in development of resistance to stressful conditions and agents including cytotoxic drugs. Study findings indicate that some but not all estrogen-positive breast cancers express Hsp27, and overexpression of Hsp27 has been associated with both good and poor prognosis. In endometrial carcinomas, the presence of Hsp27 is correlated with the degree of tumor differentiation as well as with the presence of estrogen and progesterone receptors. Studies suggest, however, that detection of Hsp27 should not be considered to be a method for identifying hormone-responsive tumors or detecting estrogen receptors. Hsp27 seems to be a biochemical marker of estrogenic endometrial response. In patients with cervical cancer, Hsp27 is predominantly expressed in well-differentiated and moderately differentiated squamous cell carcinomas. In addition, expression of Hsp27 seems to be a negative prognostic factor for gastric cancer. Different isoforms of Hsp27 have been found in lymphoid tissue of patients with acute lymphoblastic leukemia, and the protein has also been associated with viral infections. These aspects are summarized and discussed in the present review.
热休克以及其他环境和病理生理应激会刺激热休克蛋白（Hsps）的合成。这些蛋白质通过尚未完全明确的机制使细胞能够在应激条件下存活并恢复。Hsp27是一种在人类细胞（包括癌细胞和正常细胞）中发现的重要小热休克蛋白（分子量为27,000）。这种蛋白质除了在耐热性方面可能发挥的作用外，由于最近的数据表明它可能在耐药性中也起作用，因此具有特殊的临床意义。在成年人中，Hsp27特别存在于几种细胞类型中，如乳腺、子宫、宫颈、胎盘、皮肤和血小板。尽管已发现低分子量（小）热休克蛋白参与非洲爪蟾和果蝇的胚胎发育，但在人类胎儿器官中未检测到它们。热休克蛋白基因（也称为HSPB1）表达的调控一直被视为基因调控的范例，并且在原核生物和真核生物中都在积极研究。在原核生物中，主要的热休克蛋白基因受到正性和负性作用的转录因子的转录调控。在真核生物中，编码热休克蛋白的基因包含一个称为热休克元件的调控DNA基序（五聚体序列nGAAn的反向重复）。Hsp27可能作为分子伴侣并参与不同细胞调节因子的信号转导途径，并且Hsp27和其他热休克蛋白可能在对包括细胞毒性药物在内的应激条件和因子的抗性发展中起作用。研究结果表明，一些但不是所有雌激素阳性乳腺癌表达Hsp27，并且Hsp27的过表达与预后良好和不良都有关。在子宫内膜癌中，Hsp27的存在与肿瘤分化程度以及雌激素和孕激素受体的存在相关。然而，研究表明，检测Hsp27不应被视为识别激素反应性肿瘤或检测雌激素受体的方法。Hsp27似乎是雌激素子宫内膜反应的生化标志物。在宫颈癌患者中，Hsp27主要在高分化和中分化鳞状细胞癌中表达。此外，Hsp27的表达似乎是胃癌的负性预后因素。在急性淋巴细胞白血病患者的淋巴组织中发现了Hsp27的不同异构体，并且该蛋白也与病毒感染有关。本文综述总结并讨论了这些方面。
