Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma

Overexpression and localization of heat shock proteins mRNA in pancreatic carcinoma
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DOI:
10.1272/jnms.67.177
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发表时间:
2000-06-01
影响因子:
1
通讯作者:
Asano, Goro
Asano, Goro
中科院分区:
医学4区
文献类型:
--
作者:
Ogata, Masao;Naito, Zenya;Asano, Goro

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本研究采用免疫组织化学、原位杂交和逆转录聚合酶链式反应的方法,检测了热休克蛋白(HSPs)在胰腺癌组织和正常胰腺组织(包括慢性胰腺炎和正常胰腺组织)中的定位和过表达。HSP90αmRNA在胰腺癌组织中的过度表达高于正常胰腺组织。胰腺癌组织的增殖细胞核抗原标记指数也高于其他组织。提示HSP90αmRNA在肿瘤组织中的过度表达可能与细胞增殖有关。然而,HSP90β在包括胰腺癌、慢性胰腺炎和正常胰腺组织在内的所有胰腺组织中的结构性过度表达几乎相同。免疫组织化学染色显示HSP90在不同组织学类型胰腺癌中的表达存在差异。这些发现表明,HSP90α参与了癌症的发生,而HSP90β与结构构象有关。HSP90α和HSP90β似乎在含有恶性细胞的组织中发挥不同的功能。与细胞周期相关的癌基因产物P53、MDM2和WAF1在癌组织癌细胞的细胞核中表达较强。其中,MDM2在粘液性癌及癌旁粘液分泌组织中表达较强。MDM2蛋白的表达也可能与结构构象过程中的分泌系统有关,并与HSP90β相关。
In the present study we examined the localization and overexpression of heat shock proteins (hsps), mainly hsp90, in pancreatic carcinoma tissue compared with control tissue (including chronic pancreatitis and normal pancreas tissue), with the aid of immunohistochemical staining, in situ hybridization and reverse transcriptase polymerase chain reaction. Hsp90 alpha mRNA was overexpressed more highly in pancreatic carcinoma than in the control tissue. The proliferating-cell-nuclear-antigen labeling index was also high in pancreatic carcinoma tissue compared with the other tissue. These findings suggest that the overexpression of hsp90 alpha mRNA in carcinomas may be correlated with cell proliferation. However, hsp90 beta was constitutively overexpressed almost equally in all groups of pancreatic tissue including pancreatic carcinoma, chronic pancreatitis and normal pancreas tissue. Immunohistochemical staining demonstrated a differentiation in the expression of hsp90 between histological types of pancreatic carcinoma. These findings suggest that hsp90 alpha is involved in carcinogenesis and that hsp90 beta is correlated to structural conformation. Hsp90 alpha and hsp90 beta seem to perform different functions in tissue containing malignant cells. P53, MDM2 and WAF1, that were cell-cycle-related oncogene product were more strongly expressed in the nuclei of the cancer cells of the cancer tissue. Especially, MDM2 was more strongly expressed in mucinous carcinoma and the mucin secreting tissues surrounding pancreatic carcinoma tissue. The expression of MDM2 protein might also be correlated to secretion systems during structural conformation and be correlated to hsp90 beta.