Polypeptide serving as angiogenic marker and dna thereof

Abstract

A marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease and cancer, the method of detection of the marker and a diagnosis kit of the diseases are provided. Additionally, therapeutic agents of the diseases are provided. The expression of KIAA1036 is enhanced in ovarian cancer and large bowel cancer and KIAA1036 expresses in umbilical vein endothelial cell and inhibits DNA synthesis in the cells, cell migrating and lumen formation. Therefore KIAA1036 is useful as a marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer. Additionally, KIAA1036 is useful for screening of agonists, antagonists, DNA synthesis inhibitors, cell migrating inhibitors and neovascular inhibitors. The substances obtained by the screening, KIAA1036 and the antibodies are useful as therapeutic agents the above disease.

1 . A marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer, which contains a polynucleotide having a base sequence as set forth in A of 386-C of 1480 of SEQ ID NO: 1 or fragment thereof.  
     
     
         2 . A marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer, which contains a polynucleotide hybridizing under a stringent condition with a polynucleotide having a base sequence as set forth in C of 1-C of 1480 of SEQ ID NO: 1 or fragment thereof.  
     
     
         3 . A marker of  claim 1 , which contains a polynucleotide having a base sequence as set forth in C of 1-C of 1480 of SEQ ID NO: 1 or fragment thereof.  
     
     
         4 . A marker of  claim 1 , which contains a polynucleotide having a base sequence as set forth in C of 1-C of 5481 of SEQ ID NO: 1 or fragment thereof.  
     
     
         5 . A marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer, which contains a polypeptide comprising an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof.  
     
     
         6 . A marker for neovascularization, vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer, which contains a polypeptide wherein 1 or more amino acid residue(s) has a mutation(s) selected from deletion, substitution and addition in an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof.  
     
     
         7 . A marker of  claim 5 , which contains a polypeptide consisting of an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof.  
     
     
         8 . A method of detection of a marker of any one of claims  1 - 7  from a sample derived from human.  
     
     
         9 . A method of detection or assay of a marker of any one of claims  1 - 4 , which comprises the following processes and using a polynucleotide having a base sequence as set forth in A of 386-C of 1480 of SEQ ID NO: 1 or fragment thereof, 
 (a) a process that the polynucleotide and a sample are contacted, and    (b) a process that a polynucleotide binding with the polynucleotide is detected.    
     
     
         10 . A method of detection or assay of a marker of any one of claims  1 - 4 , which comprises the following processes and using a polynucleotide having a base sequence as set forth in A of 386-C of 1480 of SEQ ID NO: 1 or fragment thereof, 
 (a) a process that cDNA is prepared from a sample, and    (b) a process that cDNA is amplified with the polynucleotide fragment and detected.    
     
     
         11 . A method of detection or assay of a marker of any one of claims  5 - 7 , which comprises the following processes and using an antibody recognizing a polypeptide comprising an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof, 
 (a) a process that the antibody and a sample are contacted, and    (b) a process that the binding between the antibody and a polypeptide is detected.    
     
     
         12 . A method of detection of a disease relating to a marker of any one of claims  1 - 7 , which comprises using a method of any one of claims  9 - 11 .  
     
     
         13 . A method of detection of  claim 12 , wherein the disease is vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer.  
     
     
         14 . A diagnostic kit of a disease relating to a marker of any one of claims  1 - 7 , which comprises using a method of any one of claims  9 - 11 .  
     
     
         15 . A diagnostic kit of  claim 14 , wherein the disease is vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer.  
     
     
         16 . A screening method of a binding substance of a marker of any one of claims  5 - 7 , which comprises the following processes, 
 (a) a process that a marker of any one of claims  5 - 7  and a subject are contacted, and    (b) a process that the binding between the marker and the subject is detected.    
     
     
         17 . A kit for screening of a binding substance of  claim 16 , which contains a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 2 or fragment thereof.  
     
     
         18 . A screening method of a binding activity regulatory substance which regulates a binding between a marker of any one of claims  5 - 7  and a binding substance of the marker, which comprises the following processes, 
 (a) a process that a marker of any one of claims  5 - 7  and a binding substance of the marker are contacted in the presence or absence of a subject, and    (b) a process that a binding activity of the marker and the binding substance is compared in the presence or absence of a subject.    
     
     
         19 . A kit for screening of a binding activity regulatory substance of  claim 18 , which contains a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 2 or fragment thereof.  
     
     
         20 . A screening method of an expression regulatory substance of a marker of any one of claims  1 - 7 , which comprises the following processes, 
 (a) a process that a cell, which can express a marker of any one of claims  1 - 7 , and a subject are contacted, and    (b) a process that a change of an expression level of the marker is detected by using a method of any one of claims  9 - 11 .    
     
     
         21 . A kit for screening of an expression regulatory substance of a marker of any one of claims  1 - 7 , which comprises using the method of  claim 20 .  
     
     
         22 . A DNA synthesis inhibitor containing a polypeptide comprising an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof.  
     
     
         23 . A cell migrating activity inhibitor containing a polypeptide comprising an amino acid sequence as set forth in Met of 1-Val of 365 of SEQ ID NO: 2 or fragment thereof.  
     
     
         24 . A pharmaceutical composition which contains at least one selected from a DNA synthesis inhibitor of  claim 22 , a cell migrating activity inhibitor of  claim 23 , a polynucleotide having a base sequence as set forth in SEQ ID NO: 1 or fragment thereof, a human gene therapeutic expression vector containing polynucleotide having a base sequence as set forth in SEQ ID NO: 1 or fragment thereof, a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 2 or fragment thereof and an antibody to the polypeptide.  
     
     
         25 . A pharmaceutical composition of  claim 24 , which is a therapeutic agent for vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer.  
     
     
         26 . A method of treating vascular disease, inflammatory disease, entoptic neovascular disease, reproductive system disease, central nervous system disease or cancer, which comprises administrating a pharmaceutical composition of claims  24  or  25 .  
     
     
         27 . Use of a polynucleotide having a base sequence as set forth in SEQ ID NO: 1 and a polypeptide comprising an amino acid sequence as set forth in SEQ ID NO: 2 to produce a pharmaceutical composition of  claim 24  or  25 .