Human non-specific cross-reacting antigen (NCA), a close relative of the tumor marker human carcinoembryonic antigen (CEA), is also an in vitro homotypic intercellular adhesion molecule capable of inhibiting differentiation when expressed ectopically by myoblasts. Moreover, NCA appears to be overexpressed at the transcriptional level to a greater extent and more frequently in colorectal carcinomas than CEA. This study examines the transcriptional control mechanisms responsible for orchestrating NCA expression. The region within 284 bp upstream of the translational start site of the NCA gene was found to be capable of directing high levels of expression in functional promoter assays. Footprinting experiments identified three cis-acting elements and mobility-shift assays revealed that the first of these elements is bound by the upstream stimulating factors USF1 and USF2 while the other two are bound by the stimulatory proteins Sp1 and Sp3. No cis-acting elements corresponding 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.Keywords : transcriptional promoter; non-specific cross-reacting antigen; carcinoembryonic antigen gene family ; upstream stimulatory factors 1 and 2; stimulatory proteins 1 and 3.Human carcinoembryonic antigen (CEA) is a 180-kDa gly-many closely related molecules confounded early studies adcophosphatidylinositol-linked cell membrane glycoprotein that dressing CEA expression during carcinogenesis because the was first described over 30 years ago to be highly expressed in anti-CEA polyclonal antibodies then used to quantitate CEA exthe fetal colon and colonic carcinomas [1]. CEA has subse-pression were capable of cross-reacting with other members of quently been shown to be expressed at low levels on the apical the CEA gene family. One such serological cross-reactant is surface of epithelial cells in the colon from fetal life onward [2]. NCA [6, 7] which appears to be functionally similar to CEA. Notwithstanding this expression by normal cells, increases in Like CEA [8], NCA can mediate Ca 2ϩ -independent homotypic serum concentration of CEA have proved to be a useful clinical intercellular adhesion, but can also bind heterotypically with indicator of tumor burden on presentation and of recurrence CEA when expressed on an apposing cell membrane [9, 10]. following resection and as such CEA has been widely used as a Both CEA and NCA have been shown to block terminal differtumor marker in the management of colon cancer.entiation and the accompanying loss of cell proliferative capacMolecular cloning has revealed that the CEA gene is the ity when ectopically expressed in rat L6 myoblasts [11, 12]. prototypic member of a subfamily of the immunoglobulin super-These commonalties suggest that NCA, like CEA, may be capagene family which consists of 29 gene sequences closely linked ble of promoting the emergence of cells with the property of on the long arm of chromosome 19 [3Ϫ5]. Members ...
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