Mutation of Ha-ras Oncogene in Rat Salivary Gland Tumors Induced by DMBA / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The incidence of salivary gland tumor is approximately 2% among all head and neck tumors, of which malignant cases account for only about 5%. Much research has been performed in order to clarify the mechanism of oncogene activation, however salivary gland tumors remain understudied. We performed this study in order to characterize the ras gene in these tumors. MATERIALS AND METHODS: We treated white rats with 7, 12-dimethylbenz[a]anthracene (DMBA) and confirmed the occurrence of salivary gland tumors after ten to thirty weeks. Isolated genomic DNAs from tumor tissues were added to NIH 3T3 cells. In order to detect Ha-ras mutations, we performed a two-step PCR-RFLP and 7analyzed the mutated sequences. RESULTS: We induced salivary gland tumors by DMBA treatment in white rats. Isolated DNAs from the tumor tissues transformed the NIH 3T3 cells. Point mutations were observed in codons 12 and 61 of the Ha-ras oncogene. The total frequency of point mutations was 13.9% in DMBA-induced salivary gland tumors in rats. CONCLUSION: Our results demonstrate that a variety of cancers ras oncogene mutations were also found in salivary gland tumors. We confirmed that a point mutation of the Ha-ras oncogene in a DMBA-induced salivary gland tumor occurs at a frequency of 13.9%.

Immunohistochemical Study on the Ha-ras p21 Expression in the Gastric Carcinoma

We have investigated an immunohistochemical expression of the Human-Ha-ras oncogene product p21 in tumor cells of the primary mass and metastatic lymph nodes with different histological features of gastric cancer by using avidinbiotin complex immunoperoxidase method in formalin-fixed tissue sections from 73 cases of primary tumor mass and 23 cases of metastatic lymph node. Histologic type of the gastric cancer was classification. The results obtained were as follows: 1) Expression of Ha-ras p21 was consistantly increased in the well differentiated tubular adenocarcinoma as compared with poorly differentiated tubular adenocarcinoma (p<0.01), and was substantially decreased in mucinous carcinoma and signet ring cell carcinoma. 2) Signet ring cell carcinoma showed that positive immunoperoxidase reaction for Ha-ras p21 exhibited in the majority of immature signet ring cell with scant cytoplasm rather than in the mature signet ring cells which have abundant cytoplasm filled with mucin. This findings indicate that mucin production from the tumor cell was not correlated with activation of ras gene in the tumor tissue of gastric carcinoma. 3) In general Ha-ras p21 expression was enhanced in the metastatic tumor cells of the regional lymph node compared with primary tumor, especially it was consistantly increase in the well differentiated tubular adenocarcinoma.