Expression of drs mRNA in human lung adenocarcinomas.

The drs gene was originally isolated from a rat primary embryo fibroblast cDNA library as a suppressor gene against v-src transformation. We have previously shown that expression of drs mRNA was markedly reduced in a variety of human cancer cell lines, including those of the colon, bladder, and ovary. Furthermore, introduction of drs cDNA by retrovirus vector into these cancer cell lines caused suppression of anchorage-independent growth without affecting cell proliferation. These findings suggest that down-regulation of drs mRNA is closely correlated with expression of malignant phenotypes in development of human cancers. To clarify the correlation between down-regulation of drs mRNA and malignant tumor formation in human tumor tissues, we examined the expression of drs mRNA in well-differentiated, moderately differentiated, and poorly differentiated lung adenocarcinoma tissues by in situ mRNA hybridization. The results clearly indicated that expression of drs mRNA was markedly reduced in 5 of 5 poorly differentiated lung adenocarcinomas examined but significantly expressed in normal lung tissues and 5 of 7 moderately-differentiated and 3 of 5 well-differentiated lung adenocarcinoma tissues. Neither gross deletion nor rearrangement of the drs genome was detected in these tissues. Down-regulation of drs mRNA was also observed in human lung adenocarcinoma cell lines derived from poorly differentiated adenocarcinomas. Our results suggest that down-regulation of drs mRNA is correlated with a poor degree of differentiation and progression of lung adenocarcinoma.