Novel compositions and methods in cancer associated with altered expression of prlr

Abstract

The present invention relates to novel sequences for use in diagnosis and treatment of carcinomas, especially breast cancers. In addition, the present invention describes the use of novel compositions for use in screening methods. The invention provides compositions and methods associated with altered expression of PRLR in cancer.

1 . A recombinant nucleic acid comprising a nucleotide sequence selected from the group consisting of the sequences outlined in Table 1. 
     
     
         2 . A host cell comprising the recombinant nucleic acid of  claim 1 . 
     
     
         3 . An expression vector comprising the recombinant nucleic acid according to  claim 2 . 
     
     
         4 . A host cell comprising the expression vector of  claim 3 . 
     
     
         5 . A recombinant protein comprising an amino acid sequence encoded by a nucleic acid sequence comprising a sequence selected from the group consisting of the sequences outlined in Table 1. 
     
     
         6 . A method of screening drug candidates comprising:
 a) providing a cell that expresses a carcinoma associated (CA) gene comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1 or fragment thereof;   b) adding a drug candidate to said cell; and   c) determining the effect of said drug candidate on the expression of said CA gene.   
     
     
         7 . A method according to  claim 6  wherein said determining comprises comparing the level of expression in the absence of said drug candidate to the level of expression in the presence of said drug candidate. 
     
     
         8 . A method of screening for a bioactive agent capable of binding to an CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1, said method comprising:
 a) combining said CAP and a candidate bioactive agent; and   b) determining the binding of said candidate agent to said CAP.   
     
     
         9 . A method for screening for a bioactive agent capable of modulating the activity of an CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1, said method comprising:
 a) combining said CAP and a candidate bioactive agent; and   b) determining the effect of said candidate agent on the bioactivity of said CAP.   
     
     
         10 . A method of evaluating the effect of a candidate carcinoma drug comprising:
 a) administering said drug to a patient;   b) removing a cell sample from said patient; and   c) determining alterations in the expression or activation of a gene comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1.   
     
     
         11 . A method of diagnosing carcinoma comprising:
 a) determining the expression of one or more genes comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1, in a first tissue type of a first individual; and   b) comparing said expression of said gene(s) from a second normal tissue type from said first individual or a second unaffected individual;   wherein a difference in said expression indicates that the first individual has carcinoma.   
     
     
         12 . A method for inhibiting the activity of a CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1, said method comprising binding an inhibitor to said CAP. 
     
     
         13 . A method of treating carcinomas comprising administering to a patient an inhibitor of an CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1. 
     
     
         14 . A method of neutralizing the effect of an CA protein (CAP), wherein said CAP is encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1, comprising contacting an agent specific for said CAP protein with said CAP protein in an amount sufficient to effect neutralization. 
     
     
         15 . A polypeptide which specifically binds to a protein encoded by a nucleic acid comprising a nucleic acid selected from the group consisting of the sequences outlined in Table 1. 
     
     
         16 . A polypeptide according to  claim 15  comprising an antibody which specifically binds to a protein encoded by a nucleic acid comprising a nucleic acid sequence selected from the group consisting of the sequences outlined in Table 1. 
     
     
         17 . A biochip comprising one or more nucleic acid segments selected from the group consisting of a nucleic acid of the sequences outlined in Table 1 or fragments thereof. 
     
     
         18 . A method of diagnosing carcinoma or a propensity to carcinoma by sequencing at least one CA gene of an individual. 
     
     
         19 . A method of determining CA gene copy number comprising adding an CA gene probe to a sample of genomic DNA from an individual under conditions suitable for hybridization.