Runx3 gene showing anti-tumor activity and use thereof

Abstract

The present invention relates to a RUNX3 gene showing anti-tumor activity which is essentially involved in TGF-β-dependent programmed cell death (apoptosis) and use thereof. In addition, the present invention finds that RUNX3 gene expression is suppressed in the various gastric cancer and lung cancer cell lines. The suppression of the RUNX3 gene expression is due to hyper-methylation of CpG islands located around RUNX3 exon 1. The RUNX3 gene and its gene product of the present invention can be used effectively for the development of anti-cancer agents. The CpG islands around RUNX3 exon 1 could also be used not only for the development of anti-cancer agents which regulate the abnormal DNA methylation and thereby induce RUNX3 expression, and also for the development of methods for cancer diagnosis by measuring the abnormal DNA methylation.

1 . A method of inhibiting a tumor growth in a mammal comprising
 administering a therapeutically effective amount of an expression vector having a nucleotide encoding RUNX3 to a subject having cancer and   allowing the nucleotide to be expressed in the subject, wherein the expression of RUNX3 is suppressed in the cancer cells of said tumor.   
     
     
         2 . The method of  claim 1 , wherein the tumor is resulted from methylation of a nucleotide sequence containing CpG islands present near exon 1 of the RUNX3 gene. 
     
     
         3 . The method of  claim 1 , wherein the cancer is gastric cancer or lung cancer. 
     
     
         4 . A method of inhibiting a tumor growth in a mammal comprising
 administering a therapeutically effective amount of a RUNX3 cDNA having the nucleotide sequence SEQ. ID. NO: 1 to a subject having cancer, wherein the expression of RUNX3 is suppressed in the cancer cells of said tumor.   
     
     
         5 . The method of  claim 4 , wherein the tumor is resulted from methylation of a nucleotide sequence containing CpG islands present near exon 1 of the RUNX3 gene. 
     
     
         6 . The method of  claim 4 , wherein the cancer is gastric cancer or lung cancer. 
     
     
         7 . A method of inhibiting a tumor growth in a mammal comprising
 administering a therapeutically effective amount of a RUNX3 RNA to a subject having cancer, wherein the expression of RUNX3 is suppressed in the cancer cells of said tumor.   
     
     
         8 . The method of  claim 7 , wherein the tumor is resulted from methylation of a nucleotide sequence containing CpG islands present near exon 1 of the RUNX3 gene. 
     
     
         9 . The method of  claim 7 , wherein the cancer is gastric cancer or lung cancer. 
     
     
         10 . A method of inhibiting a tumor growth in a mammal comprising administering a therapeutically effective amount of a RUNX3 protein to a subject having cancer, wherein the expression of RUNX3 is suppressed in the cancer cells of said tumor. 
     
     
         11 . The method of  claim 10 , wherein the tumor is resulted from methylation of a nucleotide sequence containing CpG islands present near exon 1 of the RUNX3 gene. 
     
     
         12 . The method of  claim 10 , wherein the cancer is gastric cancer or lung cancer.