Nonspecific cross-reacting antigen (NCA), a member of the carcinoembryonic antigen (CEA) family, shows increased expression levels in colorectal cancer tissues. To elucidate the mechanism, we observed the effect of interferon (IFN)-gamma on the expression level of NCA mRNA in colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction assay. IFN-gamma induced NCA mRNA in three of four cell lines tested. The effect of anti-fibronectin receptor (FnR) antibody on the expression of NCA mRNA was then examined in the same manner. Colo201 and DLD-1 cells showed an increased expression level of NCA mRNA after stimulation with the antibody. On flow cytometry, FnR was expressed in only two, Colo201 and DLD-1, of the five cell lines tested. These findings indicate that IFN-gamma and anti-FnR antibody induce NCA mRNA in cultured colon cancer cell lines, suggesting that inflammatory response and cell-to-extracellular matrix interaction may be related to the increased expression of NCA mRNA in colorectal cancers in vivo.