Heterogeneity in the induction and expression of carcinoembryonic antigen-related antigens in human colon cancer cell lines.
Sodium butyrate induces morphological and biochemical changes consistent with a more differentiated phenotype in some colon cancer cell lines. These changes include increased expression of carcinoembryonic antigen (CEA) and other oncodevelopmental markers. We utilized domain-specific probes and polyclonal antibodies against CEA-related antigens to study sodium butyrate-induced expression of the CEA gene family in a villous adenoma-derived cell line, which is nontumorigenic in nude mice (VACO 235), and two colonic carcinoma cell lines known to respond to sodium butyrate exposure by phenotypic differentiation (HT-29 and LS 174T). The induction begins as quickly as 24 h after exposure and occurs primarily at a transcriptional level, although some translational control is also evident. No evidence was found for gene amplification, rearrangement, or methylation to account for the mechanism of this transcriptional control. [35S]Cysteine pulse-labeled cell lysate immunoblots and polyadenylated RNA blot hybridization suggest that increases in mRNA transcript and CEA-related glycoprotein levels are primarily due to increased synthesis rather than decreased degradation. A considerable amount of heterogeneity is seen in the biosynthesis of the CEA-related glycoproteins, with each cell line showing a distinct pattern of CEA-related antigen expression from a limited number of mRNA transcripts.
Toribara
N W
NW
Gastrointestinal Research Laboratory, Veterans Administration Medical Center, San Francisco, California 94121.
Sack
T L
TL
Gum
J R
JR
Ho
S B
SB
Shively
J E
JE
Willson
J K
JK
Kim
Y S
YS
D000230:Adenocarcinoma / Q000276:immunology*; D015152:Blotting, Northern; D015139:Blotting, Southern; D015153:Blotting, Western; D002087:Butyrates / Q000494:pharmacology; D020148:Butyric Acid; D002272:Carcinoembryonic Antigen / Q000235:genetics* / Q000302:isolation & purification; D002460:Cell Line; D003110:Colonic Neoplasms / Q000276:immunology*; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008970:Molecular Weight; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification
D002087:Butyrates; D002272:Carcinoembryonic Antigen; D004273:DNA, Neoplasm; D012334:RNA, Neoplasm; D020148:Butyric Acid