title: Hypoxia inducible factor-1α is necessary for invasive phenotype in Vegf-deleted islet cell tumors.
abstract: In the mouse model of pancreas endocrine tumor, loss of Vegf (VKO) results in dramatically decreased tumor progression; however, the residual microscopic lesions show increased invasion into surrounding exocrine tissue. Double KO mice of Vegf and hypoxia inducible factor-1α (Hif-1α) showed increased life span and suppressed tumor growth due to increased apoptosis. The increased invasiveness of tumors in VKO mice was diminished in DKO mice to the levels of wild-type mice. Compared to VKO mice, DKO mice also exhibited smaller changes in the expression levels of adhesion molecules, including E-cadherin, N-cadherin, and NCAM. These changes of adhesion molecules were not observed in the primary culture of the tumor cells under hypoxic conditions. Thus, the invasive phenotype observed under angiogenesis inhibition requires Hif-1α, but is not directly caused by acute hypoxia.
authors: Department of Biochemistry, Osaka Medical Center for Cancer and Cardiovascular Diseases, Higashinari-ku, Osaka 537-8511, Japan.
authors: Takaaki
authors: T
authors: Takeda
authors: Hiroaki
authors: H
authors: Okuyama
authors: Yasuko
authors: Y
authors: Nishizawa
authors: Shuhei
authors: S
authors: Tomita
authors: Masahiro
authors: M
authors: Inoue
mesh_terms: D007516:Adenoma, Islet Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000235:genetics; D004195:Disease Models, Animal; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009361:Neoplasm Invasiveness / Q000235:genetics; D010641:Phenotype; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; D020690:GTPase-Activating Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C490620:Ralbp1 protein, mouse; D042461:Vascular Endothelial Growth Factor A