Down-regulation of Forkhead Box M1 Transcription Factor Leads to the Inhibition of Invasion and Angiogenesis of Pancreatic Cancer Cells.
Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Yiwei Li, and Fazlul H. Sarkar
Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan
Cancer Res 2007; 67: (17). September 1, 2007
Down regulationof forkheadboxm1transcriptionfactorleadstotheinhibitionofinvasionandangiogenesisofpancreaticcancercellsppt
1. Zhiwei Wang, Sanjeev Banerjee, Dejuan Kong, Yiwei Li and Fazlul H. Sarkar Department of Pathology, Karmanos Cancer Institute, Wayne State University, Detroit, Michigan Design by ChauChanLao 2009.03 Cancer Res 2007; 67: (17). September 1, 2007 IF: 7.672
26. To determine the efficacy of FoxM1 siRNA for knockdown FoxM1 mRNA and protein Fig.1 CS : control siRNA FS : FoxM1 siRNA
27. To examine the effect of FoxM1 siRNA on cell growth of PC cells Fig.2 wikipedia.org MTT test
28. To examine the effect of FoxM1 cDNA on cell growth of PC cells CP : control plasmid FP : FoxM1 cDNA plasmid Fig.1D Fig.2
29.
30. To further investigate the growth-inhibitory effect of FoxM1 knockdown in PC cells Fig.3 Cell cycle anatysis
31. To examine the level of expression of several known G 0 -G 1 cell cycle regulatory factors Fig.4
32.
33. To investigate whether MMP-9 and MMP-2 were down-regulated by FoxM1 siRNA in PC cell lines Fig.5
34. To examine whether the down-regulation of FoxM1 could lead to a decrease in MMP-2 and MMP-9 activity in PC cells Fig.5 ELISA
35.
36. To investigate whether FoxM1 siRNA has any effect on reducing the level of uPAR (urokinase-type plasminogen activator receptor), which are able to regulate the MMP-9 activity in PC Fig.5 FoxM1 siRNA reduced uPAR gene transcription and translation
37. To test the effects of FoxM1 down-regulation on PC cell migration and invasion, using BD BioCoat Tumor Invasion Assay System www.bdbiosciences.com
41. To explore whether FoxM1 siRNA reduced VEGF activity Fig.5 FoxM1 siRNA decreased VEGF acivity (Overexpression FoxM1 increased VEGF acivity, data not shown)
42. To test whether conditioned media from FoxM1 siRNA-transfected cells could reduce the tube formation Fig.6 Matrigel in vitro HUVECs tube formation assay
45. Conclusion The down-regulation of FoxM1 could potentially be an effective therapeutic approach for the inactivation MMP-2, MMP-9, and VEGF, which is likely to result in the inhibition of cell growth, migration, invasion, angiogenesis, and metastasis of PC.