In:
Journal of Histochemistry & Cytochemistry, SAGE Publications, Vol. 54, No. 2 ( 2006-02), p. 161-169
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-β 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-β pathway were studied. To evaluate if a potential relationship with TGF-β signaling pathway exists, we correlated mRNA expression levels with the expression of TGF-βs, TGF-β receptors, and Smad-3. Finally, we analyzed the influence of TGF-β on Gata-3 expression in vitro. All pancreatic cancer samples demonstrated a marked overexpression of Gata-3 mRNA and protein. Immuno-histochemical 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-βs, TGF-β receptors, and Smad-3. TGF-β responsive cell lines showed a down-regulation of Gata-3 mRNA upon TGF-β exposure, whereas in TGF-β-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-β pathway, suggesting that Gata-3 plays a central role in human pancreatic cancer.
Type of Medium:
Online Resource
ISSN:
0022-1554
,
1551-5044
DOI:
10.1369/jhc.5A6626.2005
Language:
English
Publisher:
SAGE Publications
Publication Date:
2006
detail.hit.zdb_id:
1421306-0
SSG:
12
