Deregulated expression of genes is found in cancer cells, which may aect malignant properties, but it is unclear whether such modulation occurs allele-speci®cally. This study shows that the gene coding a4 integrin, a cell adhesion molecule, underwent allelic inactivation in a series of heterozygous murine ®brosarcoma cell lines (MST lines) with dierent metastatic potentials. P4 cells expressed the a4 integrin gene from one allele at a level comparable to that of the primary MST1 tumor, whereas the descendent lines of P4 exhibited decreased expression of both alleles. No allelic loss of DNA was observed in these cells. Other four clones derived from P4 and ®ve clones from a dierent tumor also showed such two-step inactivation. Intriguingly, the loss of expression was correlated with the acquisition of spontaneous, but not arti®cial, metastatic ability. This is consistent with the previous result of inverse relation between the expression of a4b1 integrin and the invasive potential of B16 melanoma cells. Analysis of DNA methylation and chromatin state of the a4 integrin gene failed to provide a clue to dierence between the two alleles in the cell lines. These results suggest that the allelic inactivation is a process giving loss of function to one allele, although the mechanism is unclear.
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