The biology of the 17-1A antigen (Ep-CAM).

Department of Pathology, Leiden University Medical Center, The Netherlands.
Journal of Molecular Medicine (Impact Factor: 4.77). 11/1999; 77(10):699-712. DOI: 10.1007/s001099900038
Source: PubMed

ABSTRACT The glycoprotein recognized by the monoclonal antibody (mAb) 17-1A is present on most carcinomas, which makes it an attractive target for immunotherapy. Indeed, adjuvant treatment with mAb 17-1A did successfully reduce the 5 years mortality among colorectal cancer patients with minimal residual disease. Currently the antibody is approved for clinical use in Germany, and is on its way to approval in a number of other countries. New immunotherapeutic strategies targeting the 17-1A antigen are in development or even in early-phase clinical trials. Therefore, a better understanding of the biology of the 17-1A antigen may result in improved strategies for the treatment and diagnosis of human carcinomas. In this review the properties of the 17-1A antigen are discussed concerning tumor biology and the function of the molecule. This 40-kDa glycoprotein functions as an Epithelial Cell Adhesion Molecule, therefore the name Ep-CAM was suggested. Ep-CAM mediates Ca2+-independent homotypic cell-cell adhesions. Formation of Ep-CAM-mediated adhesions has a negative regulatory effect on adhesions mediated by classic cadherins, which may have strong effects on the differentiation and growth of epithelial cells. Indeed, in vivo expression of Ep-CAM is related to increased epithelial proliferation and negatively correlates with cell differentiation. A regulatory function of Ep-CAM in the morphogenesis of epithelial tissue has been demonstrated for a number of tissues, in particular pancreas and mammary gland. The function of Ep-CAM should be taken into consideration when developing new therapeutic approaches targeting this molecule.

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    ABSTRACT: BACKGROUND The epithelial cell adhesion molecule (EpCAM) is a homophilic and Ca2+ independent adhesion molecule that is expressed de novo in squamous cell carcinoma (SCC) but is absent in the majority of healthy squamous epithelia. EpCAM expression correlates with cell proliferation and dedifferentiation along with a progression in tumorigenicity. To date, nothing is known about the molecular mechanisms responsible for the regulation of the EpCAM gene.METHODS The authors analyzed the regulation of a fragment of the EpCAM promoter.RESULTSThe analyzed fragment has significant activity in EpCAM positive cells, and it is regulated negatively by tumor necrosis factor α (TNFα). This negative regulation results in diminished mRNA expression and in the down-regulation of EpCAM protein at the cell surface in SCC cells. Both effects can be mimicked by the treatment of cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). TNFα-induced inhibition of the EpCAM expression is mediated by TNF receptor 1 through the TNF receptor-associated death domain protein (TRADD) and by the activation of nuclear factor κB (NF-κB), and it can be blocked by dominant-negative variants of TRADD and the NF-κB inhibitor, IκB. The authors provide further evidence that NF-κB represses EpCAM expression by competing for the transcriptional coactivator p300/CREB binding protein (p300/CBP).CONCLUSIONS The current results provide the first insights into the regulation of EpCAM expression, which is regulated negatively by TNFα and TPA through the activation of NF-κB. The repression may rely on the competition of NF-κB for p300/CBP histone acetyl transferase activity, because the overexpression of p300 reverts TNFα effects. Cancer 2001;92:620–8. © 2001 American Cancer Society.
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    International Journal of Cancer 07/2003; 105(2):221-5. · 6.20 Impact Factor
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    ABSTRACT: Aim of the study was to assess the diagnostic and prognostic impact of serum EpCAM levels in patients with pancreatic adenocarcinoma (PDAC).
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