Abstracts
2000 Digestive Disease Week

# 2300 Anti-Angiogenesis Effect of P53-Target Gene, BAI1 on Pancreatic Cancer.
Makoto Sunamura, Dan G. Duda, Lucian Lozonschi, Tadamichi Yokoyama, Toshimasa Yatsuoka, Fuyuhiko Motoi, Hiromune Shimamura, Kazunori Takeda, Seiki Matsuno, Sendai, Mi, Japan

Background: It is reported that the genetic alteration of p53 is associated with neovascularization during the progression of glioma to its more malignant form, glioblastoma. BAI1 which was identified as a p53-target gene, is specifically expressed in the brain, however is not expressed in gioblastoma cell lines, suggesting that BAI1 plays a significant role in angiogenesis inhibitor as a mediator of p53. We already demonstrated that BAI1 transfected glioblastoma failed to form tumor neovascularization. Purpose: In an attempt to gain insight into this effect, we checked the expression of this gene in pancreatic cancer cell lines. Furthermore, we transfected BAI1 gene to a pancreatic cancer cell line using an adenoviral vector and monitored the in vitro and in vivo growth in severe combined immune-deficient (SCID) mice. Materials and Methods: RT-PCR analysis revealed that BAI1 gene was not expressed in any of the eight pancreatic cancer cell lines. After p53 transfection using an adenoviral vector, BAI1 expression was induced in pancreatic cancer cell line (Panc1) as well as colon cancer cell lines (T84 and HT29). We transfected BAI1 gene into a pancreatic cancer cell line (Panc/BAI1) using an adenoviral vector and monitored both in vitro growth and in vivo growth using SCID mice. LacZ gene-tranfected pancreatic cancer cell line was used as control (Panc/LacZ). The in vitro growth curve of Panc/BAI1 was similar to that of Pnac/LacZ or wild type tumor cells (Panc/wild). However, the in vivo growth of Panc/BAI1 was significantly delayed as compared to Panc/ LacZ and Panc/wild. We analysed the anti-angiogenesis effect using our skinfold chamber and vital microscopy system, which allowed the accurate assessment of tumor angiogenesis. Panc/wild or Panc/LacZ in the chamber promoted the tumor neovascularization at day 14, whereas Panc/BAI1 did not. RT-PCR analysis confirmed the BAI1 expression in the Panc/BAI1 and also showed that BAI1 effect was not dependent on the endothelial cell mitogens, such as VEGF or bFGF activity. Conclusion: The expression of BAI1 gene induced tumor dormancy in human pancreatic tumors through the inhibition of tumor angiogenesis. The anti-tumor effect of p53 gene therapy would be strengthened by the combination of BAI1 pathway. The mechanism of this effect is currently under investigation.