Down-regulation of drs mRNA in human colon adenocarcinomas

We have previously reported that the drs gene, whose mRNA expression is dow n-regulated by retroviral oncogenes such as v-src and v-K-ras, has the abil ity to suppress transformation by v-src and v-K-ras in the rat cell line F2 408. We have also isolated a human homolog of this gene (h-drs) and shown t hat expression of h-drs mRNA is markedly reduced in a variety of human canc er cell lines, including those of carcinomas of the colon, bladder, and ova ry, suggesting that down-regulation of drs mRNA is correlated with the deve lopment of human cancers. To clarify the correlation between down-regulatio n of the drs gene and malignant tumor formation in human cancer tissues, we examined expression of drs mRNA in human normal tissues, colon adenoma, an d adenocarcinoma tissues by in situ hybridization. Expression of drs mRNA w as detected in most normal tissues tested, including those of the colon, bl adder, and ovary. However, drs mRNA was hardly expressed in any of the colo n adenocarcinoma tissues examined. Northern blot analyses confirmed these r esults. Neither gross deletion nor re-arrangement of the drs genome was det ected by Southern blot hybridization in these adenocarcinoma tissues. drs m RNA was significantly expressed in colon adenoma with mild atypia but downr egulated in adenomas with moderate atypia and focal carcinoma. Our results indicate that down-regulation of drs mRNA is closely correlated with develo pment of colon adenocarcinoma, suggesting a tumor-suppressor function of th e drs gene in human cancers. Int. J. Cancer 87:5-11, 2000. (C) 2000 Wiley-L iss. Inc.