ISOLATION OF MURINE AND HUMAN HOMOLOGS OF THE FISSION-YEAST DIS3(-CONTROL PROTEIN AND ITS OVEREXPRESSION IN CANCER-CELLS WITH PROGRESSIVE PHENOTYPE() GENE ENCODING A MITOTIC)

To investigate genes involved in metastasis, we used a differential di splay method to compare the Levels of gene expression in three cell Li nes derived from murine colon-adenocarcinoma 26 that show different me tastatic potentials, The results, and subsequent Northern analyses, co nfirmed that one gene was expressed most strongly in NL17, the cell Li ne with the highest experimentally metastatic potential to the lung; s trongly in NL22, the line with moderately metastatic potential; and ve ry weakly in NL4, which has no metastatic potential in recipient mice, Using this fragment as a probe, we isolated the murine cDNA as well a s its human homologue and determined their DNA sequences, The cDNA seq uences from both species contained open reading frames of 2873 nucleot ides, encoding peptides of 958 amino acids with calculated molecular w eights of approximately 109,000; the murine and human nucleotide seque nces were 90% identical, The deduced amino acid sequences of these cDN As revealed significant homology (45% identity) to the dis3(+) gene pr oduct of Schizosaccharomyces pombe, a protein thought to be essential for mitotic control in the yeast, We therefore termed the murine and h uman genes Itme (homologue to the mitotic-control gene) and HMC, respe ctively. In 7 of 13 patients with colorectal cancers and Liver metasta ses, expression of HMC was increased up to 38-fold in primary tumors a nd metastatic foci as compared to adjacent normal colorectal mucosa. A n increase in expression of HMC, its novel product likely to belong to a structurally distinct family of mitotic-control proteins, may be as sociated with malignant phenotypes of some colorectal cancers.