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

采用含DMBA/橄榄油溶液的海绵颗粒植入大鼠颌下腺，建立了大鼠涎腺癌变模型。植体手术后12周，腺鳞状细胞癌在组织学上由高度角化的鳞状上皮和小管样结构组成。采用DNA阵列法（Atras TM Rat 1.2 Clontech）检测实验性癌和正常颌下腺的基因表达。截断比和差值分别为2和背景强度水平（=4）。所有实验癌中上调基因48个，下调基因25个。癌组织中增强最多的基因是表皮脂肪酸结合蛋白，这种蛋白通常在发育不良的角化细胞中发现，其次是热休克蛋白，即著名的应激蛋白之一。一些居家基因，如-肌动蛋白，在癌组织中也有所增加。原基因群及其信号传导途径；然而，没有证据表明生长因子及其受体的mrna增加。H-ras和ras相关基因等g蛋白mRNA显著增加，一些与Raf-MEK-MRK生长信号通路相关的重要因子相关的信息也显著增加。H-ras基因的点突变也在本模型研究中发现，位于第1，第12外显子的鸟嘌呤变为腺嘌呤。该突变可改变氨基酸序列，是细胞增殖的加速因子之一，h -ras突变和过表达可能在大鼠颌下腺实验性癌变中起重要作用。

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.