Down‐regulation of drs mRNA in Colorectal Neoplasms

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Abstract
The drs gene was originally isolated as a transformation suppressor gene against the v‐src oncogene. Expression of drs mRNA is down‐regulated by retroviral oncogenes such as v‐src and v‐K‐ras in the rat cell line F2408. Expression of drs mRNA is also markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down‐regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down‐regulation of the drs gene and malignant tumor formation in human colorectal neoplasms, we examined expression of drs mRNA in a variety of colon cancer tissues by in situ hybridization. A total of 53 morphologically distinct neoplastic specimens were divided into the following five groups according to morphology: low and high grade adenoma in 7 and 12 cases, respectively (groups A, B), protruded‐type carcinoma in 16 (group C), superficial‐type carcinoma with an adenomatous component in 10 (group D) or superficial‐type carcinomas without any adenomatous component in 8 (group E). Expression of drs mRNA was detected in normal mucosa, low‐grade adenoma and most superficial‐type carcinomas without any adenomatous component. On the other hand, the rate of drs mRNA expression was significantly lower in protruded‐type adenocarcinoma and superficial‐type carcinoma with an adenomatous component. Our results indicate that down‐regulation of drs mRNA is closely correlated with carcinomas which arise from adenomatous polyps in the course of the adenoma‐carcinoma sequence, but that most carcinomas arising de novo are independent of the tumor suppressor function of the drs gene.