Bv8 nucleic acids and polypeptides with mitogenic activity

Abstract

The present invention provides methods of using Bv8 polypeptides to induce endothelial cell proliferation and to enhance endothelial cell survival. Also provided herein are methods of screening for modulators of Bv8 activity. Furthermore, methods of treatment using Bv8 polypeptides are provided.

1 - 56 . (canceled)  
     
     
         57 . A method of inhibiting angiogenesis in a tissue, endothelial cell proliferation, or endothelial cell survival, comprising administering to the cell an antagonist of a polypeptide comprising an amino acid sequence having at least 80 percent identity to SEQ ID NO:2 or SEQ ID NO:4.  
     
     
         58 . The method of  claim 57 , wherein the antagonist comprises an antisense oligonucleotide, small molecule, antibody, or antibody fragment.  
     
     
         59 . The method of  claim 58 , wherein the antibody fragment is a Fab, Fab′, F(ab′) 2 , or Fv fragment.  
     
     
         60 . The method of  claim 57 , further comprising administering an antagonist of VEGF.  
     
     
         61 . The method of  claim 57 , wherein the endothelial cells are vascular endothelial cells.  
     
     
         62 . The method of  claim 57 , wherein the endothelial cells are steroidogenic endothelial cells.  
     
     
         63 . The method of  claim 62 , wherein the endothelial cells are steroidogenic tissue cells or endocrine gland cells.  
     
     
         64 . The method of  claim 57 , wherein the tissue is steroidogenic.  
     
     
         65 . The method of  claim 64 , wherein the tissue comprises adrenal gland, reproductive, gut, or respiratory tract tissue.  
     
     
         66 . The method of  claim 65 , wherein the reproductive tissue is ovary, testis, uterus, or cervix.  
     
     
         67 . A method for treating cancer, comprising administering to the cell an antagonist of a polypeptide comprising an amino acid sequence having at least 80 percent identity to SEQ ID NO:2 or SEQ ID NO:4.  
     
     
         68 . The method of  claim 67 , wherein the cancer is hormone-dependent cancer.  
     
     
         69 . The method of  claim 68 , wherein the cancer is cancer of a reproductive tissue.  
     
     
         70 . The method of  claim 69 , wherein the reproductive tissue is testis or ovary.  
     
     
         71 . The method of  claim 67 , further comprising administering an antagonist of VEGF.  
     
     
         72 . A method of regulating fertility in a mammal, comprising administering to the mammal an antagonist of a polypeptide comprising an amino acid sequence having at least 80 percent identity to SEQ ID NO:2 or SEQ ID NO:4.  
     
     
         73 . A method of identifying an antagonist of Bv8, comprising: 
 a) contacting a candidate molecule with a polypeptide comprising an amino acid sequence having at least 80 percent identity to SEQ ID NO:2 or SEQ ID NO:4; and    b) determining if the candidate molecule inhibits endothelial cell proliferation activity of the polypeptide; and    c) identifying a candidate molecule that inhibits the endothelial cell proliferation activity of the polypeptide as an antagonist of Bv8.    
     
     
         74 . The method of  claim 73 , wherein the candidate molecule is an antibody, antibody fragment, or small molecule.