Transcriptional regulation of the non-specific 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 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.
Koops
M D
MD
McGill Cancer Centre, McGill University, Montréal, Québec, Canada.
Thompson
J
J
Zimmermann
W
W
Stanners
C P
CP
D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D001483:Base Sequence; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D015815:Cell Adhesion Molecules; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism*; D017931:DNA Primers; D004268:DNA-Binding Proteins; D015972:Gene Expression Regulation, Neoplastic; D018257:Helix-Loop-Helix Motifs; D006801:Humans; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D005810:Multigene Family; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D051720:Upstream Stimulatory Factors
D000951:Antigens, Neoplasm; D002272:Carcinoembryonic Antigen; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D004268:DNA-Binding Proteins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C497181:USF1 protein, human; C497184:USF2 protein, human; D051720:Upstream Stimulatory Factors