Expression of cyclin G1 in tumors

Abstract

A method of treating a tumor (in particular osteosarcoma or Ewing's sarcoma) in a host by administering to a host or to the tumor cells an agent which inhibits cyclin G1 protein in an amount effective to inhibit cyclin G1 protein in tumor cells of the host. The agent may be an antisense polynucleotide which is complementary to at least a portion of a polynucleotide encoding cyclin G1 protein, or an antibody or fragment or derivative thereof which recognizes cyclin G1 protein. Also contemplated within the scope of the present invention are (i) the immortalization of cell lines by transducing cells with a polynucleotide encoding cyclin G1 protein; (ii) increasing the receptiveness of cells to retroviral infection by transducing cells with a polynucleotide encoding cyclin G1 protein; and (iii) the detection of cancer by detecting cyclin G1 protein or a polynucleotide encoding cyclin G1 protein in cells. In addition, the present invention provides expression vehicles, such as, for example, retroviral vectors and adenoviral vectors, which include polynucleotides which encode agents which inhibit cyclin G1 protein, and expression vehicles which include a polynucleotide encoding cyclin G1 protein.

What is claimed is:  
     
         1 . A method of treating a tumor in a host comprising: 
 administering to a host an agent which inhibits cyclin G1 protein, said agent being administered in amount effective to inhibit cyclin G1 protein in tumor cells of said host.    
     
     
         2 . The method of  claim 1  wherein said agent is an antisense polynucleotide which is complementary to at least a portion of a polynucleotide encoding cyclin G1 protein.  
     
     
         3 . The method of  claim 1  wherein said agent is an antibody or fragment or derivative thereof which recognizes cyclin G1 protein.  
     
     
         4 . The method of  claim 3  wherein said antibody is a single-chain antibody.  
     
     
         5 . The method of  claim 3  wherein said antibody is a monoclonal antibody.  
     
     
         6 . The method of  claim 3  wherein said antibody is a polyclonal antibody.  
     
     
         7 . The method of  claim 2  wherein said antisense polynucleotide is administered to said host by transducing tumor cells of said host with an expression vehicle including a polynucleotide encoding an antisense polynucleotide which is complementary to at least a portion of a polynucleotide encoding cyclin G1 protein.  
     
     
         8 . The method of  claim 7  wherein said expression vehicle is a retroviral vector.  
     
     
         9 . The method of  claim 1  wherein said tumor is a cancerous tumor.  
     
     
         10 . The method of  claim 9  wherein said cancerous tumor is osteogenic sarcoma.  
     
     
         11 . The method of  claim 9  wherein said cancerous tumor is Ewing's sarcoma.  
     
     
         12 . The method of  claim 3  wherein said antibody or fragment of derivative thereof which recognizes cyclin G1 protein is administered to said host by transducing tumor cells of said host with an expression vehicle including a polynucleotide encoding said antibody or fragment or derivative thereof which recognizes cyclin G1 protein.  
     
     
         13 . The method of  claim 12  wherein said expression vehicle is a retroviral vector.  
     
     
         14 . A method of immortalizing non-tumor cells comprising: 
 transducing said non-tumor cells with a polynucleotide encoding cyclin G1 protein or a derivative or analogue thereof.    
     
     
         15 . The method of  claim 14  wherein said polynucleotide encoding cyclin G1 or a derivative or analogue thereof is contained within a retroviral vector.  
     
     
         16 . A method of enhancing transduction of cells with a retroviral vector that includes a polynucleotide encoding a therapeutic agent, comprising: 
 transducing said cells with a first expression vehicle that includes a polynucleotide encoding cyclin G1 protein, wherein said first expression vehicle is not a retroviral vector; and    transducing said cells with a second expression vehicle that includes a polynucleotide encoding a therapeutic agent, said second expression vehicle being a retroviral vector.    
     
     
         17 . The method of  claim 16  wherein said first expression vehicle is an adenoviral vector.  
     
     
         18 . The method of  claim 16  wherein said cells are transduced with said first expression vehicle and said second expression vehicle in vivo.  
     
     
         19 . The method of  claim 16  wherein said cells are transduced with said first expression vehicle and said second expression vehicle in vitro.  
     
     
         20 . The method of  claim 16  wherein said cells are transduced with said first expression vehicle prior to transduction of said cells with said second expression vehicle.  
     
     
         21 . The method of  claim 16  wherein said cells are transduced with said first expression vehicle and said second expression vehicle concurrently.  
     
     
         22 . An expression vehicle including a polynucleotide encoding an agent selected from the group consisting of (i) an agent which inhibits cyclin G1 protein; and (ii) cyclin G1 protein.  
     
     
         23 . The expression vehicle of  claim 22  wherein said expression vehicle is a viral vector.  
     
     
         24 . The vector of  claim 23  wherein said vector is a retroviral vector.  
     
     
         25 . The vector of  claim 24  wherein said agent is an agent which inhibits cyclin G1 protein.  
     
     
         26 . The vector of  claim 25  wherein said agent which inhibits cyclin G1 protein is an antisense polynucleotide which is complementary to at least a portion of a polynucleotide encoding cyclin G1 protein.  
     
     
         27 . The vector of  claim 25  wherein said agent which inhibits cyclin G1 protein is an antibody or fragment or derivative thereof which recognizes cyclin G1 protein.  
     
     
         28 . The vector of  claim 24  wherein said agent is cyclin G1 protein.  
     
     
         29 . The vector of  claim 23  wherein said vector is an adenoviral vector.  
     
     
         30 . The vector of  claim 29  wherein said agent is an agent which inhibits cyclin G1 protein.  
     
     
         31 . The vector of  claim 30  wherein said agent which inhibits cyclin G1 protein is an antisense polynucleotide which is complementary to at least a portion of a polynucleotide encoding cyclin G1 protein.  
     
     
         32 . The vector of  claim 30  wherein said agent which inhibits cyclin G1 protein is an antibody or fragment or derivative thereof which recognizes cyclin G1 protein.  
     
     
         33 . The vector of  claim 29  wherein said agent is cyclin G1 protein.  
     
     
         34 . A producer cell which produces the retroviral vector of  claim 24 .  
     
     
         35 . A method of detecting cancer, comprising: 
 contacting cells with an agent which binds to (i) cyclin G1 protein and/or (ii) a polynucleotide encoding cyclin G1 protein; and determining binding of said agent to said cyclin G1 protein and/or said polynucleotide encoding cyclin G1 protein.    
     
     
         36 . The method of  claim 35  wherein said agent is a polynucleotide which hybridizes to a polynucleotide encoding cyclin G1 protein.  
     
     
         37 . The method of  claim 35  wherein said agent is an antibody or a fragment or derivative thereof which recognizes cyclin G1 protein.  
     
     
         38 . The method of  claim 35  wherein said cancer is osteogenic sarcoma.  
     
     
         39 . The method of  claim 35  wherein said cancer is Ewing's sarcoma.  
     
     
         40 . A method of preventing restenosis, comprising: 
 administering to a host an agent which inhibits cyclin G1 protein, said agent being administered in an amount effective to prevent restenosis in a host.