In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2602-2602
Abstract:
The FoxM1 transcription factor promotes the pathogenesis of several malignancies. However, little is known about its expression and function in papillary thyroid cancers (PTC). In the present study we investigated the role of FoxM1 in the pathogenesis of PTC in a large series of PTC in a tissue micro array (TMA) format followed by studies using PTC cell lines and nude mice. Our data showed that expression of FoxM1 was over expressed in 28.4 % (141/496) of PTC and significantly associated with activated AKT (p & lt;0.0001) and matrix metalloproteinase-9 (MMP-9) expression (p=0.0004). FoxM1 over expression was also strongly associated with antiapoptotic markers, XIAP (p=0.0024), and Bcl-Xl (p=0.0014). In vitro data using PTC cell lines showed that inhibition of FoxM1 by thiostrepton resulted in inhibition of proliferation and induction of apoptosis in a dose dependent manner. In addition, thiostrepton treatment caused downregulation of SKP2, and consequent increase expression of p21 in PTC cell lines. We also found that down-regulation of FoxM1 reduced the expression of MMP-2, MMP-9 and vascular endothelial growth factor, resulting in the inhibition of migration, invasion, and angiogenesis in PTC cells. Furthermore, pharmacological inhibition of FoxM1 or siRNA targeted against FoxM1 triggered caspase dependent apoptosis in PTC cells. Finally, treatment of PTC cell line xenografts with thiostrepton resulted in growth inhibition of tumors in nude mice via downregulation of FoxM1 and MMP9. Altogether, our results suggest that FoxM1 and its associated signaling pathway may be a potential target for therapeutic intervention for treatment of PTC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2602. doi:10.1158/1538-7445.AM2011-2602
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2011-2602
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2011
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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