Induction of carcinoembryonic-antigen-gene expression in human colorectal carcinoma by sodium butyrate.
The effect of sodium butyrate on the expression of the carcinoembryonic-antigen (CEA) gene was studied in two poorly differentiated colorectal-carcinoma cell lines (Clone-A and MIP-101) and in one well-differentiated cell line (LS-174T); A.T.C.C. no. CCL 188). Northern-blot and dot-blot analyses indicated a steady increase in CEA mRNA from day 4 to a maximal level by day 14 after these cells were exposed to 2 mM-sodium butyrate. Studies using nuclear run-off assays followed by dot-blot hybridization to a partial CEA cDNA clone demonstrated that specific increases in gene transcription rates (3-fold in MIP-101, 4-fold in LS-174T and 6-fold in Clone-A) are not sufficient to account for the observed increases in CEA mRNA abundance. Further studies showed that CEA-specific transcripts have a half-life of about 60-80 min, and treatment with sodium butyrate increased the stability of CEA-specific transcripts to about 340 min in LS-174T cells and to about 500 min in Clone-A cells. We conclude that the induction of the CEA-gene expression by sodium butyrate in colorectal-cancer cells is mediated by both transcriptional and post-transcriptional mechanisms, with CEA mRNA stability as one of the major check-points.
Saini
K
K
Department of Surgery, New England Deaconess Hospital, Harvard Medical School, Boston, MA 02115.
Steele
G
G
Thomas
P
P
D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002272:Carcinoembryonic Antigen / Q000235:genetics*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003001:Cloning, Molecular; D015179:Colorectal Neoplasms; D004273:DNA, Neoplasm / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D002087:Butyrates; D002272:Carcinoembryonic Antigen; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D020148:Butyric Acid