Studies on suppression of transformation in primary rat embryo fibroblasts

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On searching for transformation suppressor genes in primary cells, we isolated a novel gene, drs (doenregulated by v-src), which was expressed in normal rat fibroblast cells but completely suppressed in the cells transformed by the v-src gene, from a cDNA library of REF.The molecular cloned cDNA was about 1.8kb in size, containing an open reading frame composed of 464 amino acid residues. Homology search of drs protein revealed that this protein had one transmembrane domain and three consensus repeats (CR) which were conserved as various numbers of CR in extracellular domain of the selsctin family. Expression of drs mRNA was also down-regulated by serum stimulation of G0-arrested normal rat cells. To clarify the biological function of the drs gene, we introduced the drs gene linked to potent promoter into normal rat cell line and examined the sensitivity to transformation by the v-src oncogene. Rat cell lines expressing exogenous drs gene showed lower efficiency of v-src transformation, indicating a transformation suppressor function of the drs gene. The drs gene was also downregulated in human colon cancer cell lines and ectopic expression of this gene suppressed the ability of prolifelation in these cancer cell lines, suggesting a role in the genesis of human cancers.