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Aberrant gata-3 expression in human pancreatic cancer

Gata-3 has been shown to specifically alter its expression patterns in different types of cancers. Recent evidence suggests that an interference of Gata-3 exists in the TGF-beta signaling pathway. To determine the role of Gata-3 in pancreatic cancer, pancreatic cancer samples were analyzed in compar...

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Main Authors: Gulbinas, Antanas (Author) , Berberat, Pascal O. (Author) , Dambrauskas, Zilvinas (Author) , Giese, Thomas (Author) , Giese, Nathalia (Author) , Autschbach, Frank (Author) , Kleeff, Jörg H. (Author) , Meuer, Stefan (Author) , Büchler, Markus W. (Author) , Friess, Helmut (Author)
Format: Article (Journal)
Language:English
Published: February 1, 2006
In: Journal of histochemistry & cytochemistry
Year: 2006, Volume: 54, Issue: 2, Pages: 161-169
ISSN:1551-5044
DOI:10.1369/jhc.5A6626.200
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1369/jhc.5A6626.200
Verlag, lizenzpflichtig, Volltext: https://journals.sagepub.com/doi/epub/10.1369/jhc.5A6626.2005
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Author Notes:Antanas Gulbinas, Pascal O. Berberat, Zilvinas Dambrauskas, Thomas Giese, Nathalia Giese, Frank Autschbach, Joerg Kleeff, Stefan Meuer, Markus W. Büchler, and Helmut Friess
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Summary:Gata-3 has been shown to specifically alter its expression patterns in different types of cancers. Recent evidence suggests that an interference of Gata-3 exists in the TGF-beta signaling pathway. To determine the role of Gata-3 in pancreatic cancer, pancreatic cancer samples were analyzed in comparison to normal pancreatic tissues. Furthermore, four different pancreatic cancer cell lines with different alterations of the TGF-beta pathway were studied. To evaluate if a potential relationship with TGF-beta signaling pathway exists, we correlated mRNA expression levels with the expression of TGF-betas, TGF-beta receptors, and Smad-3. Finally, we analyzed the influence of TGF-beta on Gata-3 expression in vitro. All pancreatic cancer samples demonstrated a marked overexpression of Gata-3 mRNA and protein. Immunohistochemical staining revealed strong and persistent cytoplasmic Gata-3 immunoreactivity in cancer cells. In an electrophoretic mobility shift assay, a disturbed nuclear translocation was confirmed. The expression of Gata-3 showed a significant correlation with the expression of TGF-betas, TGF-beta receptors, and Smad-3. TGF-beta responsive cell lines showed a downregulation of Gata-3 mRNA upon TGF-beta exposure, whereas in TGF-beta-unresponsive cell lines, Gata-3 mRNA expression persisted at high levels. Furthermore, strong specific upregulation of Gata-3 impaired nuclear translocation and its cooperative action with the TGF-beta pathway, suggesting that Gata-3 plays a central role in human pancreatic cancer.
Item Description:Gesehen am 09.06.2021
Physical Description:Online Resource
ISSN:1551-5044
DOI:10.1369/jhc.5A6626.200

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