ISOLATION OF A NOVEL GENE SHOWING REDUCED EXPRESSION IN METASTATIC COLORECTAL-CARCINOMA CELL-LINES AND CARCINOMAS

To investigate genes involved in metastatic stages of cancer, we analy zed expression of mRNAs in three cell lines derived from murine colon adenocarcinoma 26 by means of a differential display method, Each of t hese lines exhibits distinct metastatic characteristics. Among many ba nds representing different expression patterns in the display, we conf irmed by northern analysis that a gene corresponding to one amplified fragment, termed grm2 (gene related to metastasis 2), was expressed mo re abundantly in NL4, the derivative with the lowest metastatic potent ial, than in cell lines NL17, an experimentally metastatic derivative, and in NL22, a spontaneously metastatic derivative, Using the grm2 fr agment as a probe, we isolated murine cDNA clones and subsequently hum an cDNA clones corresponding to the GRM2 gene, The human and mouse hom ologues both encode proteins of 600 amino-acid residues, which show we ak homologies to proteins belonging to the myosin family, When we exam ined the expression levels of this novel gene in human colon cancers a nd in corresponding metastatic foci, we found that in more than half o f these tissues, expression was significantly reduced in association w ith malignant potential, Our results imply that in humans the GRM2 gen e product may regulate the metastatic phenotype of some colorectal can cers.