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

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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.