Methods of detection and treatment of breast cancer

Abstract

Novel methods of detecting and treating breast cancer are described.

What is claimed is:  
     
         1 . A method of inhibiting breast cancer cell growth comprising supplying Csk Homologous Kinase to breast cells whereby breast cancer cell growth is inhibited.  
     
     
         2 . The method of  claim 1 , wherein a nucleic acid sequence encoding Csk Homologous Kinase, or a biologically active fragment, analog or derivative thereof, is supplied to the breast cells, wherein the nucleic acid sequence encoding Csk Homologous Kinase or a biologically active fragment, analog or derivation thereof, is expressed in the breast cell.  
     
     
         3 . The method of  claim 2  wherein Csk Homologous Kinase is supplied to the cell by a nucleic acid construct containing a nucleic acid sequence encoding Csk Homologous Kinase or a biologically active fragment, analog or derivative thereof, wherein the construct is introduced into the breast cell and Csk Homologous Kinase is expressed.  
     
     
         4 . The method of  claim 1 , wherein Csk Homologous Kinase protein or a biologically active Csk Homologous Kinase peptide is supplied to breast cells.  
     
     
         5 . The method of  claim 4 , wherein the Csk Homologous Kinase protein or peptide is supplied to the cell by introducing into the cell a liposome containing the Csk Homologous Kinase or Csk Homologous Kinase peptide.  
     
     
         6 . The method of  claim 5 , wherein the liposome is contained in a topical formulation and is introduced to the breast cells by topical application.  
     
     
         7 . A Csk Homologous Kinase derivative produced by altering native or variant Csk Homologous Kinase DNA within the Csk Homologous Kinase SH2 domain to optimize its association with ErbB-2.  
     
     
         8 . The derivative of  claim 7 , wherein the mutation is a substitution of one or more amino acids between amino acid 127 and 150 of SEQ ID NO: 1.  
     
     
         9 . The derivative of  claim 7 , wherein the mutation is in an amino acid residue conserved between csk and c-src, but not conserved between csk and Csk Homologous Kinase.  
     
     
         10 . The derivative of  claim 9 , wherein the mutation is a substitution of amino acid 129 of SEQ ID NO: 1.  
     
     
         11 . The derivative of  claim 9 , wherein the mutation is a substitution from said residue to the corresponding residue conserved in csk and c-src.  
     
     
         12 . A derivative of Csk Homologous Kinase comprising a mutation which is a substitution of one or more amino acids between amino acid 127 and 150 of SEQ ID NO: 1.  
     
     
         13 . The derivative of  claim 12 , wherein the mutation is in an amino acid residue conserved between csk and c-src, but not conserved between csk and Csk Homologous Kinase.  
     
     
         14 . The derivative of  claim 12 , wherein the mutation is a substitution of amino acid 129 of SEQ ID NO: 1.  
     
     
         15 . The derivative of  claim 12 , wherein the mutation is a substitution from said residue to the corresponding residue conserved in csk and c-src.  
     
     
         16 . The derivative of  claim 12 , wherein the mutation is in an amino acid residue conserved between csk, c-src and Csk Homologous Kinase.  
     
     
         17 . The derivative of  claim 12  wherein the mutation is a substitution of amino acid 147 of SEQ ID NO: 1  
     
     
         18 . A Csk Homologous Kinase derivative produced by altering native or variant Csk Homologous Kinase DNA within the Csk Homologous Kinase SH2 domain to inhibit its association with ErbB-2.  
     
     
         19 . A CHK analog that mimics the binding of the derivative of  claim 7 .  
     
     
         20 . A CHK analog that mimics the binding of the derivative of  claim 12 .  
     
     
         21 . A pharmaceutical composition that contains an effective amount of the CHK derivative of  claim 7 .  
     
     
         22 . A pharmaceutical composition that contains an effective amount of the CHK derivative of  claim 12 .  
     
     
         23 . A method of identifying a biologically active CHK analog with greater biological activity than native CHK, comprising: 
 a. contacting ErbB-2 with the CHK analog to be tested for biological activity, under conditions sufficient for binding of ErbB-2 by the CHK analog;    b. contacting ErbB-2 with native CHK, under conditions sufficient for binding of ErbB-2 by the native CHK; and    c. comparing the binding of ErbB-2 by the CHK analog with the binding of ErB-2 by the native CHK.    
     
     
         24 . The method of  claim 23 , wherein the CHK analog is the analog of  claim 19 .  
     
     
         25 . The method of  claim 23 , wherein the CHK analog is an analog of  claim 20 .  
     
     
         26 . The CHK analog identified by the method of  claim 23 .  
     
     
         27 . A method of identifying a biologically active CHK derivative with greater biological activity than native CHK, comprising: 
 a. contacting ErbB-2 with the CHK derivative to be tested for biological activity, under conditions sufficient for binding of ErbB-2 by the CHK derivative;    b. contacting ErbB-2 with native CHK, under conditions sufficient for binding of ErbB-2 by the native CHK; and    c. comparing the binding of ErbB-2 by the CHK derivative with the binding of ErB-2 by the native CHK.    
     
     
         28 . The method of  claim 27 , wherein the CHK derivative is the derivative of  claim 7 .  
     
     
         29 . The method of  claim 27 , wherein the CHK derivative is the derivative of  claim 12 .  
     
     
         30 . The CHK derivative identified by the method of  claim 27 .  
     
     
         31 . A CHK analog that binds to ErbB-2 and enhances the activity of CHK.  
     
     
         32 . A pharmaceutical composition that comprises an effective amount of a CHK analog, wherein the CHK analog binds to ErbB-2 and enhances the activity of CHK.