The role of Heat shock protein in the process of cartinogeneis and progression of human ovarian cancer

在以往的研究中，我们报道了Rb或P53基因产物在卵巢癌细胞系中可以与细胞内热休克蛋白结合，与人细胞的癌变有一定的相关性。本研究通过对人卵巢癌组织中热休克蛋白P53或Rb基因产物的免疫组织化学分析，发现P53蛋白表达与肿瘤进展有关，而Rb产物及其磷酸化酶CDC-2在癌变的早期过程中表达。用新研制的抗HAP73单抗(杂交瘤13：737,1994)检测卵巢组织中hap73的表达，正常卵巢组织、良性肿瘤36%、交界性肿瘤77%、早期卵巢癌68%、晚期卵巢癌65%均为阴性。Rb蛋白也以类似的方式表达，交界性肿瘤最常见。但在c-…中，P53的表达频率随肿瘤的分级而增加。更多的癌变和进展。70 kDa热休克蛋白在卵巢癌发生过程中过度表达，并可能在肿瘤细胞表面表达，是机体免疫应答过程中重要的肿瘤排斥反应抗原。我们报道了在H-ras转化成纤维肉瘤细胞系WFB的W31细胞表面表达的抗原之一是热休克蛋白，尤其是HSC 73，CE3+4-8-T细胞受体α-β-杀伤细胞(DNT)对W31的细胞毒作用被认为是hSC73的配基，这种免疫反应也在人卵巢癌细胞系中检测到。进一步分析这些细胞内肽在大鼠胚胎细胞和W31肿瘤细胞之间的相互作用，hsc73抗体可抑制这些多肽所含的细胞毒作用，该反应可阻断该反应。这意味着这些多肽在肿瘤排斥反应过程中hsc73相关细胞毒性的免疫反应中起着非常重要的作用。较少

In the previous studies, we reported Rb or p53 geen products could be bind with intracellular heat shock proteins in ovarian cancer cell lines, with some corelation with carcinogenesis in human cells.In this studywe performed a immunohistochemical analysis of heat shock proteinp53 or Rb gene products in human ovarian cancerwhich showed p53 protein expression was associated with cancer progression, but Rb products and their phosphorylating enzyme cdc-2 was expressed in the early process of carcinogenesis. Further, by using newly produced anti-hap 73 monoclonal antibody (Hybridoma 13 : 737,1994), hap73 expressions were examined with ovarian tisuues ; negative for normal ovarial tissues, 36% of bening tumors, 77% of borderline tumors, and 68% in early stage ovarian cancer, 65% in advanced ovarian cancer. And Rb proteins were also expressd in the similar fashion, at borderline tumors most frequently. But, the frequency of p53 expression was increased with the grade of malignancies during c … More arcinogenesis and progression. And as the prognostic factor, only p53 expression was associated with poor prognosis of ovarian cancer patients.70kDa heat shock proteins overexpress in the process of carcinogenesis and may be expressed on the surface, as an important tumor-rejection antigen during hostimmune responses. We reported that one of the antigens expressed on the surface of H-ras transformed fibrosarcoma cell line, W31 from rat fetal fibroblast WFB was heat shock protein, especially hsc 73, and the cytotoxicity of CE3+4-8-T cell receptor alphabeta-killer (DNT) cells for W31 was recognized as the ligand of hsc73 with certain celluar nascent of mutant peptides from the tumor cell, and this immunologic reaction was also detected in the system of human ovarian cancer cell lines. Further analysis of these intracellular peptides were performed between rat fetal cells and W31 tumor cells, cytotoxicity included with peptides was inhibited with hsc73 antibody and proteinase treatment was blocked with this reaction. This means these peptides are very important in the immunoreaction of hsc73-ralated cytotoxicity in the process of tumor rejection. Less