TRANSCRIPTIONAL REGULATION OF THE NONSPECIFIC CROSS-REACTING ANTIGEN GENE, A MEMBER OF THE CARCINOEMBRYONIC ANTIGEN GENE FAMILY UP-REGULATED IN COLORECTAL CARCINOMAS

Human non-specific cross-reacting antigen (NCA), a close relative of t he tumor marker human carcinoembryonic antigen (CEA), is also an in vi tro homotypic intercellular adhesion molecule capable of inhibiting di fferentiation when expressed ectopically by myoblasts. Moreover, NCA a ppears to be overexpressed at the transcriptional level to a greater e xtent and more frequently in colorectal carcinomas than CEA. This stud y examines the transcriptional control mechanisms responsible for orch estrating NCA expression. The region within 284 bp upstream of the tra nslational start site of the NCA gene was found to be capable of direc ting high levels of expression in functional promoter assays. Footprin ting experiments identified three cis-acting elements and mobility-shi ft assays revealed that the first of these elements is bound by the up stream stimulating factors USF and USF2 while the other two are bound by the stimulatory proteins Sp1 and Sp3. No cis-acting elements corres ponding to CEA footprint FP4 or the silencer CEA FP5 were detected in the NCA promoter, which may contribute to the differential expression of NCA versus CEA in tumorigenesis.