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Induction of carcinoembryonic-antigen-gene expression in human colorectal carcinoma by sodium butyrate.

ABSTRACT: 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.

SUBMITTER: Saini K

PROVIDER: S-EPMC1149736 | biostudies-other | 1990 Dec

REPOSITORIES: biostudies-other

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Carcinoembryonic antigen-targeted photodynamic therapy in colorectal cancer models.

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| S-EPMC6906275 | biostudies-literature

Carcinoembryonic antigen-like substances of human urothelial carcinomas. Isolation of components from pathological urine and comparison with colorectal carcinoma antigens.

Project description:Urines of several patients with urothelial carcinomas contain inhibitors of the immunoreaction between carcinoembryonic antigen derived from human colorectal carcinomas and monospecific goat antiserum raised against the antigen. These inhibitors range in approximate molecular weights from less than 1000 to several millions, and two have been isolated by a combination of extraction, gel filtration and electrophoretic procedures. These are respectively a macromolecular aggregate, component UCEA-3, which is excluded by Sepharose 4B, and a glycoprotein(s) component, UCEA-1, with mean molecular weight (2x10(5)) similar to that of carcinoembryonic antigen. Comparison of the properties of component UCEA-1 and carcinoembryonic antigen on gel filtration, electrophoresis, immunoelectrophoresis and density gradient ultracentrifugation indicates that these substances of similar molecular size and net charge differ in some immunochemical properties.

| S-EPMC1166300 | biostudies-other

c-KIT-ERK1/2 signaling activated ELK1 and upregulated carcinoembryonic antigen expression to promote colorectal cancer progression.

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| S-EPMC7894012 | biostudies-literature

Sodium butyrate promotes generation of human induced pluripotent stem cells through induction of the miR302/367 cluster.

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| S-EPMC3730377 | biostudies-literature

Serum- and oncoprotein-mediated induction of a gene with sequence similarity to the gene encoding carcinoembryonic antigen.

Project description:We describe the molecular identification of a gene, designated T1, whose expression in mouse NIH 3T3 cells is strongly induced by the Ha-ras(EJ) and v-mos oncogenes and by serum. The T1 gene encodes a 38.5-kDa protein, as predicted from its primary sequence and shown by in vitro translation. The protein was processed at its amino terminus and extensively modified by N-linked glycosylation in vitro in the presence of microsomal vesicles. Sequence comparison of T1 with the MIPSX data base (Max-Planck-Institut für Biochemie, Martinsried/Munich) revealed similarity to the human carcinoembryonic antigen, a tumor marker which is overexpressed in colon adenocarcinomas and in fetal tissues. Considerable sequence similarity has also been observed to the short conserved region of other proteins which, like carcinoembryonic antigen, are encoded by members of the immunoglobulin gene superfamily.

| S-EPMC297699 | biostudies-other

Effect of Sodium Butyrate on <i>LHX1</i> mRNA Expression as a Transcription Factor of HDAC8 in Human Colorectal Cancer Cell Lines.

Project description:BackgroundLHX1 is an important transcription factor for the HDAC8 gene. The aim of this study was to investigate the effect of Sodium Butyrate (SB), as a histone deacetylase inhibitor, on the expression of LHX1 gene in colorectal cancer cell lines.MethodsHT-29 and HCT-116 cell lines were treated with 6.25 to 200 mM concentrations of SB at 24, 48, and 72 hr. The cytotoxicity effect on cell viability was evaluated by MTT assay. The 50% Inhibiting Concentration (IC50) was determined graphically. Quantitative real-time PCR was performed to investigate the LHX1 mRNA expression level.ResultsOur study revealed that SB inhibited the proliferation of these cell lines in a concentration and time-dependent manner. The IC50 values for HT-29 cell line were 65, 18.6, and 9.2 mM after 24, 48, and 72 hr of treatment, respectively. The IC50 values for HCT-116 cell line were 35.5, 9.6, and 10 mM after 24, 48, and 72 hr of treatment, respectively. Furthermore, real-time PCR findings demonstrated that the LHX1 mRNA expression in treated HT-29 cell line significantly increased in comparison with untreated cells (p<0.05). However, in treated HCT-116 cell line, SB led to a significant decrease in the level of LHX1 mRNA (p<0.05), as compared to untreated cells.ConclusionIn this study, different effects of SB on LHX1 mRNA expression level were revealed in two distinct human colorectal cancer cell lines.

| S-EPMC6925397 | biostudies-literature

Carcinoembryonic antigen is the preferred biomarker for in vivo colorectal cancer targeting.

Project description:BackgroundColorectal cancer-specific biomarkers have been used as molecular targets for fluorescent intra-operative imaging, targeted PET/MRI, and selective cytotoxic drug delivery yet the selection of biomarkers used is rarely evidence-based. We evaluated sensitivities and specificites of four of the most commonly used markers: carcinoembryonic antigen (CEA), tumour-associated glycoprotein-72 (TAG-72), folate receptor-? (FR?) and Epithelial growth factor receptor (EGFR).MethodsMarker expression was evaluated semi-quantitatively in matched mucosal and colorectal cancer tissues from 280 patients using immunohistochemistry (scores of 0-15). Matched positive and negative lymph nodes from 18 patients were also examined.ResultsMarkers were more highly expressed in tumour tissue than in matched normal tissue in 98.8%, 79.0%, 37.1% and 32.8% of cases for CEA, TAG-72, FR? and EGFR, respectively. Carcinoembryonic antigen showed the greatest differential expression, with tumours scoring a mean of 10.8 points higher than normal tissues (95% CI 10.31-11.21, P<0.001). Similarly, CEA showed the greatest differential expression between positive and negative lymph nodes. Receiver operating characteristic analyses showed CEA to have the best sensitivity (93.7%) and specificity (96.1%) for colorectal cancer detection.ConclusionCarcinoembryonic antigen has the greatest potential to allow highly specific tumour imaging and drug delivery; future translational research should aim to exploit this.

| S-EPMC3593555 | biostudies-literature

Sodium butyrate and dexamethasone promote exocrine pancreatic gene expression in mouse embryonic stem cells.

Project description:AimThe feasibility of inducing endocrine pancreatic differentiation of embryonic stem (ES) cells has been well documented. However, whether ES cells possess the potential for exocrine pancreatic differentiation requires further exploration. Here, we investigated whether sodium butyrate and glucocorticoids were conducive to the exocrine pancreatic differentiation of ES cells.MethodsE14 mouse ES cells were cultured in suspension to form embryoid bodies (EBs). These EBs were cultured in differentiating medium containing varying concentrations of sodium butyrate. The effects of activinA and dexamethasone (Dex) on exocrine differentiation were also explored. Finally, the combination of sodium butyrate, activinA, and Dex was used to promote the differentiation of exocrine pancreatic cells. Specific exocrine pancreatic gene expression was detected by reverse transcription polymerase chain reaction (RT-PCR) and amylase expression was examined by immunofluorescence staining. Flow cytometry analysis was also performed to determine the percentage of amylase-positive cells after the treatment with activinA, sodium butyrate, and Dex.ResultsExposure of ES cells to 1 mmol/L sodium butyrate for 5 days promoted exocrine pancreatic gene expression. Further combination with Dex and other pancreatic-inducing factors, such as activinA, significantly enhanced the mRNA and protein levels of exocrine pancreatic markers. Additionally, flow cytometry revealed that approximately 17% of the final differentiated cells were amylase-positive.ConclusionThese data indicate that the exocrine pancreatic differentiation of ES cells can be induced by activinA, sodium butyrate, and Dex, providing a potential tool for studying pancreatic differentiation and pancreas-related diseases.

| S-EPMC4007190 | biostudies-literature

Sodium butyrate inhibits osteogenesis in human periodontal ligament stem cells by suppressing smad1 expression.

Project description:BackgroundButyrate is a major subgingival microbial metabolite that is closely related to periodontal disease. It affects the proliferation and differentiation of mesenchymal stem cells. However, the mechanisms by which butyrate affects the osteogenic differentiation of periodontal ligament stem cells (PDLSCs) remain unclear. Here, we investigated the effect of sodium butyrate (NaB) on the osteogenic differentiation of human PDLSCs.MethodsPDLSCs were isolated from human periodontal ligaments and treated with various concentrations of NaB in vitro. The cell counting kit-8 assay and flow cytometric analysis were used to assess cell viability. The osteogenic differentiation capabilities of PDLSCs were evaluated using the alkaline phosphatase activity assay, alizarin red staining, RT-PCR, western blotting and in vivo transplantation.ResultsNaB decreased PDLSC proliferation and induced apoptosis in a dose- and time-depend manner. Additionally, 1 mM NaB reduced alkaline phosphatase activity, mineralization ability, and the expression of osteogenic differentiation-related genes and proteins. Treatment with a free fatty acids receptor 2 (FFAR2) antagonist and agonist indicated that NaB inhibited the osteogenic differentiation capacity of PDLSCs by affecting the expression of Smad1.ConclusionOur findings suggest that NaB inhibits the osteogenic differentiation of PDLSCs by activating FFAR2 and decreasing the expression of Smad1.

| S-EPMC9297574 | biostudies-literature

A novel Carcinoembryonic Antigen (CEA)-Targeted Trimeric Immunotoxin shows significantly enhanced Antitumor Activity in Human Colorectal Cancer Xenografts.

Project description:Immunotoxins are chimeric molecules, which combine antibody specificity to recognize and bind with high-affinity tumor-associated antigens (TAA) with the potency of the enzymatic activity of a toxin, in order to induce the death of target cells. Current immunotoxins present some limitations for cancer therapy, driving the need to develop new prototypes with optimized properties. Herein we describe the production, purification and characterization of two new immunotoxins based on the gene fusion of the anti-carcinoembryonic antigen (CEA) single-chain variable fragment (scFv) antibody MFE23 to α-sarcin, a potent fungal ribotoxin. One construct corresponds to a conventional monomeric single-chain immunotoxin design (IMTXCEAαS), while the other one takes advantage of the trimerbody technology and exhibits a novel trimeric format (IMTXTRICEAαS) with enhanced properties compared with their monomeric counterparts, including size, functional affinity and biodistribution, which endow them with an improved tumor targeting capacity. Our results show the highly specific cytotoxic activity of both immunotoxins in vitro, which was enhanced in the trimeric format compared to the monomeric version. Moreover, the trimeric immunotoxin also exhibited superior antitumor activity in vivo in mice bearing human colorectal cancer xenografts. Therefore, trimeric immunotoxins represent a further step in the development of next-generation therapeutic immunotoxins.

| S-EPMC6690998 | biostudies-literature

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