Gene expression during Experimental Carcinogenesis of Rat Submandibular Gland DNA Array Study

大鼠颌下腺 DNA 阵列研究实验性癌变过程中的基因表达

基本信息

批准号：
14571803
负责人：
SUMITOMO Shinichiro
金额：
$ 2.11万
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：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571803/
关键词：
Salivary Gland Tumor Rat DNA Array Oncogene Growth Factor ras 癌遺伝子マウス

项目摘要

A model study for salivary carcinogenesis was made by implantation of a sponge pellet, which containing DMBA/olive oil solution into the rat submandibular gland. Twelve weeks after implant operation, adeno-squamous cell carcinoma histologically consisting of both hyper keratinized squamous epithelium and tubulo-duct-like structures.Gene expression of experimental carcinoma and normal submandibular gland were examined using DNA array method (Atras TM Rat 1.2 Clontech). Cut off ratio and differences were decided as twice and background intensity level (=4) respectively.Up regulated genes in all experimental carcinoma were 48 genes and down regulated were 25 genes. Most enhanced gene in the cancer tissue was for epidermal fatty acid-binding protein, which usually found in dysplastic keratinocytes and the next was for heat shock proteins as known one of the famous stress proteins. Some house keeping genes such as beta-actin also increased in cancer tissue. In the group of protoncogenes and their signal conduction pass way ; although, there are no evidence of increasing of mRNAs of growth factors and their receptors. G-proteins mRNA such as H-ras and ras-related gene were increased dramatically and some messages which cording important factors acting on Raf-MEK-MRK growth signaling pass way. Point mutation of H-ras gene also found in this model study that a guanine at exon 1, corden 12 changes into an adenine. This mutation could change amino-acid sequence and had been reported that one of the accelerate factor in cell proliferation.H-ras mutation and overexpression may play an important role for experimental carcinogenesis in rat submandibular gland.

唾液致癌的模型研究是通过植入海绵颗粒进行的，海绵颗粒含有DMBA/橄榄油溶液到大鼠下颌腺中。植入物操作后十二周，在组织学上腺癌癌在组织学上由高角膜激素化的鳞状上皮和肾小管造成的结构组成。使用DNA阵列方法（ATRAS TM RAP RAP RAT 1.2 CLONTECH）检查了实验性癌和正常下颌腺的gene表达。切断的比率和差异分别为两次和背景强度水平（= 4）。所有实验性癌的调节基因均为48个基因，而下调的基因为25个基因。癌组织中最大的基因是表皮脂肪酸结合蛋白的，通常在发育异常的角质形成细胞中发现，而下一种是热休克蛋白，是著名的应激蛋白之一。一些饲养基因（例如β-肌动蛋白）的房屋在癌组织中也增加了。在质子基因及其信号传导的过程中；虽然，没有证据表明生长因子及其受体的mRNA增加。 G蛋白mRNA（例如H-RAS和RAS相关的基因）显着增加，并且一些信息将作用于Raf-Mek-MRK生长信号传递的重要因素缠绕起来。 H-RAS基因的点突变在这项模型研究中也发现，外显子1处的鸟嘌呤12变成腺嘌呤。该突变可能会改变氨基酸序列，并据报道说，细胞增殖的加速因子之一。H-RAS突变和过表达可能对大鼠下颌腺实验性致癌作用起重要作用。