ALLELE-SPECIFIC INACTIVATION OF THE ALPHA-4 INTEGRIN GENE-EXPRESSION IN FIBROSARCOMA CELL-LINES AND RELEVANCE FOR SPONTANEOUS METASTASIS

Deregulated expression of genes is found in cancer cells, which may af fect malignant properties, but it is unclear whether such modulation o ccurs allele-specifically. This study shows that the gene coding alpha 4 integrin, a cell adhesion molecule, underwent allelic inactivation in a series of heterozygous murine fibrosarcoma cell lines (MST lines) with different metastatic potentials. P4 cells expressed the alpha 4 integrin gene from one allele at a level comparable to that of the pri mary MST1 tumor, whereas the descendent lines of P4 exhibited decrease d expression of both alleles, No allelic loss of DNA was observed in t hese cells, Other four clones derived from P4 and five clones from a d ifferent tumor also showed such two-step inactivation, Intriguingly, t he loss of expression was correlated with the acquisition of spontaneo us, but not artificial, metastatic ability, This is consistent with th e previous result of inverse relation between the expression of alpha 4/beta 1 integrin and the invasive potential of B14 melanoma cells. An alysis of DNA methylation and chromatin state of the alpha 4 integrin gene failed to provide a clue to difference between the two alleles in the cell lines, These results suggest that the allelic inactivation i s a process giving loss of function to one allele, although the mechan ism is unclear.