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Gene expressions and cellular adhesion in experimental carcinogenesis of rat submandibular gland

大鼠颌下腺实验性癌变中的基因表达和细胞粘附

基本信息

批准号：
09671937
负责人：
SUMITOMO Shinichiro
金额：
$ 2.3万
依托单位：
Asahi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671937/
关键词：
rat submandibular gland carcinogenesis PCNA keratin calponin FGF c-erbB-2 RT-PCR 免疫組織化学

项目摘要

A process of carcinogenesis in rat submandibular gland (SMG), following the 2%DMBA containing sponge pellet insertion, was studied by the use of several histochemical markers and RT-PCR. K8.12 cytokeratin, epidermal growth factor, endothelin-3 and S-100 protein were used for the imunohistochemical markers of salivary gland duct. Calponin was used for the imunohistochemical marker of mioepithelial cells. Proliferating cell nuclear antigen imunohistochemistry and ィイD13ィエD1H-thymidine auto-radiograph were used to obtain proliferating potential. Basis fibroblast growth factor (bFGF) and its receptor (FGFr), and c-erbB-2 were studied as oncogene products.During the carcinogenesis, proliferating cells were found in several kinds of ductal cells, though acinar compartment including myoepithelial cells showed no or minimal proliferating protential. In the histological patterns of carcinoma in rat SMG, the differentiation and/or conduction of modified myoepithelial cells may deeply influenced to form tubro-ductal structures in adenocarcinoma. There were no calponin positive modified myoepithelial cells found in squamous cell carcinoma, through in the adenomacarcinoma, they were arranged in the basal layer of the proliferating and dysplastic tubro-ductal structures.In the variation of oncogene products during carinogenesis, bFGF and FGFr were enhanced their immunohistochemical expression in the tumor nest and coexisted in the same tumor cells. These result may suggest that, bFGF may stimulate carcinogenesis by autocrin and/or paracrin pathway. Furthermore, a progression of carcinogenesis brought to increase of c-erbB-2 mRNA level. RT-PCR product of c-erbB-2 was absent in normal SMG and 3 weeks of carnogenesis but showed harlf and all cases in 6 weeks and in 12 weeks specimens, respectively. Excessive c-erbB-2 prot-oncogene product may be one of a course for SMG carcinogenesis following DMBA administration.

应用组织化学标记和RT-PCR技术，研究了含2%DMBA海绵颗粒的大鼠下颌下腺（SMG）癌变过程。以K8.12细胞角蛋白、表皮生长因子、内皮素-3和S-100蛋白为涎腺导管的免疫组化标记物。以Calponin作为微上皮细胞的免疫组化标记。用增殖细胞核抗原免疫组化法和放射自显影法检测细胞增殖能力。癌基因产物为碱性成纤维细胞生长因子（bFGF）及其受体（FGFr）和c-erbB-2，在癌变过程中，多种导管细胞均有增殖，而腺泡区室包括肌上皮细胞无或仅有极少量的增殖。在大鼠SMG癌的组织学类型中，修饰的肌上皮细胞的分化和/或传导可能受到深刻影响，从而形成腺癌中的管状导管结构。在癌形成过程中癌基因产物的变化中，bFGF和FGFr在癌巢中的免疫组化表达增强，并在同一肿瘤细胞中共存。这些结果提示bFGF可能通过自分泌和/或旁分泌途径促进肿瘤的发生。随着癌变进程的进行，c-erbB-2 mRNA表达水平逐渐升高。RT-PCR结果显示，正常SMG和成肌3周标本中c-erbB-2表达阴性，而6周和12周标本中c-erbB-2表达阳性。过量的c-erbB-2原癌基因产物可能是SMG致癌的过程之一。