Use of anti-prolactin agents to treat proliferative conditions

Abstract

The present invention relates to variant forms of human prolactin which act as antagonists at the prolactin receptor, and to the use of such variants in the treatment of human cancers and proliferative disorders, including both benign and malignant diseases of the breast and prostate.

1 . A method of inhibiting proliferation of a prostate cancer cell which expresses a prolactin receptor, comprising exposing the cell to an effective concentration of a variant of human prolactin, wherein the variant comprises a substitution of the glycine at position 129.  
     
     
         2 . The method of  claim 1 , wherein the variant of human prolactin comprises a substitution of the glycine at position 129 with arginine.  
     
     
         3 . The method of  claim 1 , which is used in the treatment of prostate cancer in a subject in need of such treatment.  
     
     
         4 . The method of  claim 3 , wherein the variant of human prolactin is administered to the subject as part of a combined therapy regimen.  
     
     
         5 . The method of  claim 4 , wherein the combined therapy regimen comprises the administration of an anti-androgen.  
     
     
         6 .- 14 . (canceled)  
     
     
         15 . A method for inducing cellular apoptosis in a cell expressing a prolactin receptor, comprising exposing the cell to an effective concentration of a variant of human prolactin, wherein the variant comprises a substitution of the glycine at position 129.  
     
     
         16 . The method of  claim 15 , wherein the variant of human prolactin comprises a substitution of the glycine at position 129 with arginine.  
     
     
         17 . (canceled)  
     
     
         18 . A method for identifying a compound capable of modulating prolactin receptor activity, comprising: 
 a. contacting a compound to a cell that expresses the prolactin receptor;    b. measuring the level of apoptosis in the cell; and    c. comparing the level of apoptosis obtained in (b) to the level obtained in the absence of the compound;    such that if the level obtained in (b) differs from that obtained in the absence of a compound, a compound capable of modulating prolactin receptor activity has been identified.    
     
     
         19 . The method of  claim 18 , wherein the compound increases the level of apoptosis in the cell.  
     
     
         20 . The method of  claim 18 , wherein the compound decreases the level of apoptosis in the cell.  
     
     
         21 . The method of  claim 15 , wherein the cell is a breast or prostate cancer cell.  
     
     
         22 . A method of inhibiting proliferation of a breast cancer cell which expresses a prolactin receptor, comprising exposing the cell to an effective concentration of a variant of human prolactin, wherein the variant comprises a substitution of the glycine at position 128.  
     
     
         23 . A method of treating a prostate cancer cell which expresses a prolactin receptor, comprising exposing the cell to an effective concentration of a variant of human prolactin wherein the variant comprises a substitution of the glycine at position 129.