Disease relevance of TACSTD1

• Molecular clones for the GA733-2 antigen were isolated from a colorectal carcinoma cell line cDNA library using the high-efficiency COS cell expression system [1].
• Defined by monoclonal antibody GA733, the GA733-2 antigen is a cell surface 40-kDa glycoprotein associated with human carcinomas of various origins [1].
• Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer [2].
• Correlation of COX-2 and Ep-CAM overexpression in human invasive breast cancer and its impact on survival [3].
• These results suggest the potential of VV GA733-2 as a candidate vaccine for patients with CRC, possibly in combination with recombinant GA733-2-expressing adenovirus, which has been shown to induce cytolytic antibodies and T cells as well as tumor protective effects in mice [4].
• In this study of untreated breast cancer patients, Ep-CAM overexpression was associated with poor survival in the entire cohort and in the subgroup of triple-negative breast cancer [5].
• The fluorescence-activated cell sorting-isolated EpCAM(+) HCC cells displayed hepatic cancer stem cell-like traits including the abilities to self-renew and differentiate [6].

Psychiatry related information on TACSTD1

• We report a case of acute Datura stramonium intoxication in a 6-year-old boy from Khamis Mushayt, KSA, who presented with restlessness, hallucinations and mydriasis 8 hours after ingesting the seeds of Datura plant [7].

High impact information on TACSTD1

• Intraepithelial T lymphocytes express LAIR-1 and thus may interact with Ep-CAM present on human intestinal epithelium [8].
• Colorectal carcinoma invasion inhibition by CO17-1A/GA733 antigen and its murine homologue [9].
• Twenty-five patients with metastatic gastrointestinal adenocarcinoma received one to four infusions (400 mg) of murine monoclonal antibody CO17-1A [10].
• Phase I trial of multiple large doses of murine monoclonal antibody CO17-1A. II. Pharmacokinetics and immune response [11].
• Ep-CAM overexpression in breast cancer as a predictor of survival [12].

Chemical compound and disease context of TACSTD1

• We examined the hypothesis that DNA methylation prevents the amplification of the TROP1 gene by treating JAR choriocarcinoma cells with 5-azacytidine to decrease DNA methylation [13].
• Monoclonal antibody CO17-1A, which has specificity for colorectal and pancreatic carcinomas, was radiolabeled with the pure beta emitter, 90Y, by either the cyclic diethylenetriaminepentaacetic acid (DTPA) anhydride technique or by a site-specific bifunctional chelate technique using 1-(p-aminobenzyl)DTPA (p-NH2-Bz-DTPA) [14].
• The SAL-treated compared with the control group was characterized by decreased basal and insulin-stimulated EE (P < 0.01), increased protein EE (P < 0.01), and hypersensitivity to insulin in terms of suppression of EGP (P < 0.05) and M value (P < 0.01) [15].
• Neither gamma-interferon nor 5-fluorouracil were able to increase EGP40 expression in human ovarian cancer cells in vitro [16].
• The ex vivo elimination of ovarian cancer cells in tumor preparations from 21 patients was monitored by flow cytometry using Ep-CAM/CA-125 double-labeling or Ep-CAM single-labeling combined with propidium iodide uptake of cells [17].

Biological context of TACSTD1

• The two genes with the highest inverse association with invasion, TACSTD1 and CLDN3, are involved with cell adhesion and cell-cell interactions, respectively [18].
• At the amino acid sequence level, GA733-2 was found to be greater than 99% identical to the previously described KSA antigen defined by monoclonal antibody KS1/4 [1].
• Analysis of glycosylation sites showed that GA733-2 antigen contained N-linked carbohydrate but that no O-linked carbohydrate groups were detected [19].
• Because oligomerization of some CAMs regulates cell adhesion and signal transduction, the correlation between GA733 oligomeric state and cell-cell adhesion was investigated [20].
• The loss of p53 was shown to induce loss of DNA methylation in the TROP1 gene, a human cancer-expressed locus that undergoes amplification when hypomethylated [21].

Anatomical context of TACSTD1

• Epithelial glycoprotein is a member of a family of epithelial cell surface antigens homologous to nidogen, a matrix adhesion protein [22].
• The cell surface antigen, epithelial glycoprotein, defined by the monoclonal antibody HEA 125, is expressed on virtually all epithelial cell membranes but not on mesodermal or neural cell membranes [22].
• The cDNA encoding epithelial glycoprotein was isolated by HEA 125 antibody enrichment of colon tumor cDNA expressed transiently in COS cells [22].
• A murine cDNA encodes a pan-epithelial glycoprotein that is also expressed on plasma cells [23].
• VV GA733-2 induced Ag-specific antibodies that reacted predominantly to unknown epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with murine peritoneal macrophages as effector cells [4].

Associations of TACSTD1 with chemical compounds

• The GA733-2 antigen is a cell surface glycoprotein highly expressed on most human gastrointestinal carcinoma and at a lower level on most normal epithelia [19].
• Immunohistochemical staining of formalin-fixed, paraffin-embedded tumor specimens from which primary OSPC cultures were derived further confirmed differential expression of CD24 and TROP-1/Ep-CAM markers on OSPC vs. NOVA [24].
• Seventeen contiguous NH2-terminal amino acids were identified and coincided exactly with residues 82-98 of the GA733-2 protein cloned by Szala et al [25].
• RESULTS: EpCAM is consistently expressed in the distal nephron on normal renal epithelium [26].
• Pretreatment of human EGP with pronase, trypsin, 2-ME, or heating did not interfere with the ability of human EGP to inhibit the binding of human erythrocytes to porcine Kupffer cells [27].
• Silenced Ep-CAM gene in cancer cells was enriched for hypermethylated histone 3 lysine 9 [28].

Regulatory relationships of TACSTD1

• Mutations of TP53 induce loss of DNA methylation and amplification of the TROP1 gene [21].
• Ad5 GA733-2 induced Ag-specific Abs that reacted predominantly to CO17-1A- and GA733-unrelated epitopes on the Ag and lysed Ag-positive CRC targets in conjunction with effector cells [29].
• Reverse transcriptase polymerase chain reaction analysis of BM mononuclear cells revealed that the 9C4(+) erythroblast population but not the 9C4(-) fraction expressed Ep-CAM mRNA [30].
• The tumour-associated antigen EpCAM upregulates the fatty acid binding protein E-FABP [31].
• E-FABP is a major target of c-Myc and was rapidly upregulated upon induction of EpCAM [31].

Other interactions of TACSTD1

• The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR) [8].
• Using a gene-amplification assay in vivo, we demonstrate that the loss of p53 leads to a demethylation-dependent TROP1 gene amplification [21].
• RESULTS: Preclinical and initial clinical studies with monoclonal antibodies CO17-1A, BW494/32 and anti-epidermal growth factor receptor (EGFR) have been conducted, and various targets suitable for immunotherapy have been identified involving new molecular and gene technology [32].
• RESULTS: The presence of an inflammatory reaction surrounding the tumor (P = .07), eosinophilic infiltration (P = .16), positive immunostaining for Rb (P = .02), negative immunostaining for Ep-CAM (P = .13), and amplification of CCND1 and EMS1 (P = .05) correlated with nodal metastasis [33].
• PVA and SFTPB are particularly powerful in tumors of squamous and adenocarcinoma histologies, respectively, whereas TACSTD1 is a good general marker for NSCLC metastasis [34].

Analytical, diagnostic and therapeutic context of TACSTD1

• Molecular cloning of cDNA for the carcinoma-associated antigen GA733-2 [1].
• In this study, the disulfide-bonding pattern of the GA733-2 antigen was determined using matrix-assisted laser desorption/ionization mass spectrometry and N-terminal sequencing of purified tryptic peptides treated with 2-[2'-nitrophenylsulfonyl]-3-methyl-3-bromoindolenine or partially reduced and alkylated [19].
• To evaluate the relation of COX-2 and Ep-CAM overexpression and its prognostic significance, we performed a retrospective study on 212 breast cancer patients with a median follow-up time of 10.5 years [3].
• Northern blot analysis shows that transcription of KSA can be detected in RNA isolated from normal colon but not in RNA isolated from normal lung, prostate, or liver [35].
• EpCAM protein expression in tumors and matched morphologically normal renal tissues was evaluated using anti-EpCAM immunohistochemistry [26].

References