Cell proliferation inhibitory proteins and polynucleotides, antisense polynucleotides to the polynucleotides, cell proliferation inhibitors using the foregoing, cancer diagnostic agents, cancer therapeutic agents and compositions for gene therapy

Abstract

The genes the expression of which is reduced or disappeared in immortal cells including cancer cells are isolated, their DNA sequences are determined, the genes are expressed to produce cell proliferation inhibitory proteins, and the genes and the proteins are utilized as agents for diagnosis or treatment, including the genetic diagnosis of or the gene therapy of diseases such as cancer.

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         20 . A method of inhibiting cell proliferation, which comprises introducing a polynucleotide comprising at least one of the DNA sequences set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or the DNA sequence encoding the amino acid sequence set forth in SEQ ID NO:1 in the Sequence Listing into cells.  
     
     
         21 . The method according to  claim 20 , wherein said polynucleotide consists essentially of the DNA sequence set forth in SEQ ID NO:2.  
     
     
         22 . A method of treating cancer, which comprises administering a polynucleotide comprising at least one of the DNA sequences set forth in SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, or the DNA sequence encoding the amino acid sequence set forth in SEQ ID NO:1 in the Sequence Listing in a patient in need of treatment.  
     
     
         23 . The method according to  claim 22 , wherein said polynucleotide consists essentially of the DNA sequence set forth in SEQ ID NO:2 in the Sequence Listing.  
     
     
         24 . The method according to  claim 23 , wherein the DNA is contained in a viral vector.  
     
     
         25 . The method according to  claim 24 , wherein the viral vector is an Adenovirus vector.  
     
     
         26 . The method according to  claim 22 , wherein the cancer is lung cancer, hepatocellular carcinoma, esophageal cancer or gastric cancer.  
     
     
         27 . A method of inhibiting cell proliferation, which comprises introducing a polynucleotide encoding REIC protein.  
     
     
         28 . A method of treating cancer which comprises administering to a patient in need of treatment a polynucleotide encoding REIC protein.  
     
     
         29 . A novel invention selected from the group consisting of: 
 (a) a protein comprising an amino acid sequence derivable from the substitution or the deletion of one or more amino acids in the amino acid sequence set forth in SEQ ID NO:1 in the Sequence Listing, or from the addition of one or more amino acids to the amino acid sequence set forth in SEQ ID NO:1 in the Sequence Listing, said protein possessing cell proliferation inhibitory activity;    (b) a polynucleotide comprising a DNA sequence derivable from the substitution or the deletion of one or more DNA in a DNA sequence selected from the group consisting of the DNA sequence set forth in SEQ ID No:2 in the Sequence Listing, the DNA sequence set forth in the SEQ ID NO:3 in the Sequence Listing and the DNA sequence set forth in SEQ ID NO:4 in the Sequence Listing, or from the addition of one or more DNA to a DNA sequence selected from the group consisting of the DNA sequence set forth in SEQ ID NO:2 in the Sequence Listing, the DNA sequence set forth in SEQ ID NO:3 in the Sequence Listing and the DNA sequence set forth in SEQ ID NO:4 in the Sequence Listing, said polynucleotide possessing cell proliferation inhibitory activity;    (c) RNA encoded by a DNA sequence selected from the group consisting of the DNA sequence set forth in SEQ ID NO:2 in the Sequence Listing, the DNA sequence set forth in SEQ ID NO:3 in the Sequence Listing sand the DNA sequence set forth in SEQ ID NO:4 in the Sequence Listing.    (d) an antisense polynucleotide comprising an antisense DNA to a DNA comprising a DNA sequence selected from the group consisting of the DNA sequence set forth in SEQ ID NO:2 in the Sequence Listing, the DNA sequence set forth in SEQ ID NO:3 in the Sequence Listing and the DNA sequence set forth in SEQ ID NO:4 in the Sequence Listing, or a derivative thereof; and    (e) a composition for gene therapy comprising as a therapeutic gene, a polynucleotide comprising a DNA sequence selected from the group consisting of the DNA sequence set forth in SEQ ID NO:2 in the Sequence Listing, the DNA sequence set forth in SEQ ID NO:3 in the Sequence Listing and the DNA sequence set forth in SEQ ID NO:4 in the Sequence Listing.