Aberrant gata-3 expression in human pancreatic cancer

• Verfasst von: Gulbinas, Antanas [VerfasserIn]
• Verfasst von: Berberat, Pascal O. [VerfasserIn]
• Verfasst von: Dambrauskas, Zilvinas [VerfasserIn]
• Verfasst von: Giese, Thomas [VerfasserIn]
• Verfasst von: Giese, Nathalia [VerfasserIn]
• Verfasst von: Autschbach, Frank [VerfasserIn]
• Verfasst von: Kleeff, Jörg H. [VerfasserIn]
• Verfasst von: Meuer, Stefan [VerfasserIn]
• Verfasst von: Büchler, Markus W. [VerfasserIn]
• Verfasst von: Friess, Helmut [VerfasserIn]
• Titel: Aberrant gata-3 expression in human pancreatic cancer
• Verf.angabe: Antanas Gulbinas, Pascal O. Berberat, Zilvinas Dambrauskas, Thomas Giese, Nathalia Giese, Frank Autschbach, Joerg Kleeff, Stefan Meuer, Markus W. Büchler, and Helmut Friess
• E-Jahr: 2006
• Jahr: February 1, 2006
• Umfang: 9 S.
• Teil: volume:54
• Teil: year:2006
• Teil: number:2
• Teil: pages:161-169
• Teil: extent:9
• Fussnoten: Gesehen am 09.06.2021
• Titel Quelle: Enthalten in: Journal of histochemistry & cytochemistry
• Ort Quelle: London [u.a.] : Sage Publ., 1953
• Jahr Quelle: 2006
• Band/Heft Quelle: 54(2006), 2, Seite 161-169
• ISSN Quelle: 1551-5044
• DOI: doi:10.1369/jhc.5A6626.2005
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adult
• Sach-SW: Aged
• Sach-SW: Aged, 80 and over
• Sach-SW: Cell Line, Tumor
• Sach-SW: Cell Nucleus
• Sach-SW: Cytoplasm
• Sach-SW: Electrophoretic Mobility Shift Assay
• Sach-SW: Female
• Sach-SW: GATA3 Transcription Factor
• Sach-SW: Humans
• Sach-SW: Immunohistochemistry
• Sach-SW: Male
• Sach-SW: Microscopy, Confocal
• Sach-SW: Middle Aged
• Sach-SW: Neoplasm Staging
• Sach-SW: Pancreas
• Sach-SW: Pancreatic Neoplasms
• Sach-SW: Protein Transport
• Sach-SW: RNA, Messenger
• Sach-SW: Signal Transduction
• Sach-SW: Transforming Growth Factor beta
• Sach-SW: Up-Regulation
• K10plus-PPN: 1760150614

Abstract

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.