Gene expressions in experimental carcinogenesis of rat submandibular gland and salivary gland tumors of human being

大鼠颌下腺和人类唾液腺肿瘤实验性癌变中的基因表达

基本信息

批准号：
12671841
负责人：
SUMITOMO Shinichiro
金额：
$ 2.24万
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671841/
关键词：
salivarv gland human rat salivaly gland tumors DNA array oncogene ras calponin 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 RT-PCR-SSCP. Furthermore, clinical cases of salivary gland tumors and obstructive sialoadenitis were studied by the use of immunohistochemistry and DNA array.In the experimental carcinogenesis, presence of H-ras mRNA was demonstrated in normal SMG and all experimental cases. Mutant H-ras gene was observed by PCR-SSCP in 1 of 15 cases at 5 weeks after DMBA treatment, 5 cases at 6 weeks specimen, 13 cases at 9 weeks and all 15 cases at 12 weeks specimen. Point mutation of H-ras gene was found cordon 1 exon 12 and GGA was changed to GAA. It has been reported that the point mutation substitutes glysine for glutamin may activate oncogenicity of H-ras proto-oncogene. These results suggested that the point mutation of H-ras gene might induce malignant transformation of experimental carcinoma.Immunohistochemical localization of Cal and metaltyonein (MT) was examined in normal salivary gland and obstructive sialoadenitis. In the normal gland, Cal was localized in myioepithelial cells and MT was found in ductal basal cells. Reactive myoepithelial cells and outer layer cells of duct-like structures in sialoadenitis expressed both Cal and MT staining. These cells in obstructive sialoadenitis may demonstrate cellular characteristics of both myoepithelial bells and ductal basalcells.DNA array analysis for obstructive sialoadenitis, pleomorphic adenoma and cyst adenoma was carried out. In these neoplasms, amplification of mRNA of transcription factors and apoptosis inhibitors was observed. In sialoadenitis, amplification of mRNA of some component of immunoglobulin and platelet derived growth factor. Though, the influences of amplification of these mRNA to the tumor genesis and tumor progression are still unclear.

通过使用RT-PCR-SSCP，研究了大鼠下颌腺（SMG）的致癌过程（SMG）。此外，通过使用免疫组织化学和DNA阵列研究了唾液腺肿瘤和阻塞性唾液腺炎的临床病例。在实验性癌变中，在正常SMG和所有实验病例中证明了H-RAS mRNA的存在。在DMBA治疗后的5周中，PCR-SSCP在15例中的1例中有1例观察到突变的H-RAS基因，在6周样本时5例，在9周时13例，所有15例在12周样本时。发现H-RAS基因的点突变发现Cordon 1外显子12，然后将GGA更改为GAA。据报道，该点突变替代Glysine来激活H-Ras原癌基因的致癌性。这些结果表明，H-RAS基因的点突变可能诱导实验性癌的恶性转化。在正常的唾液腺和阻塞性唾液中炎中检查了CAL和Metaltyonin（MT）的免疫组织化学定位。在正常腺体中，CAL位于肌上皮细胞中，并在导管基底细胞中发现MT。唾液腺炎中的反应性肌上皮细胞和管道样结构的外层细胞表达了CAL和MT染色。这些细胞在阻塞性唾液腺炎中可能表明肌上皮铃和导管基底层的细胞特征。DNA阵列分析用于阻塞性唾液腺炎，多态腺瘤和囊肿腺瘤。在这些肿瘤中，观察到转录因子和凋亡抑制剂的mRNA扩增。在唾液腺炎中，免疫球蛋白和血小板衍生生长因子的某些成分的mRNA扩增。但是，这些mRNA对肿瘤起源和肿瘤进展的扩增的影响尚不清楚。