Breast Specific Genes and Proteins

Abstract

Human breast specific gene polypeptides and DNA (RNA) encoding such polypeptides and a procedure for producing such polypeptides by recombinant techniques is disclosed. Also disclosed are methods for utilizing such polynucleotides or polypeptides as a diagnostic marker for breast cancer and as an agent to determine if breast cancer has metastasized. Also disclosed are antibodies specific to the breast specific gene polypeptides which may be used to target cancer cells and be used as part of a breast cancer vaccine. Methods of screening for antagonists for the polypeptide and therapeutic uses thereof are also disclosed.

1 . An isolated polynucleotide comprising a member selected from the group consisting of: 
 (a) a polynucleotide encoding the same polypeptide as the polynucleotide of  FIG. 1  (SEQ ID NO: 1);    (b) a polynucleotide encoding the same mature polypeptide as a human gene having a coding portion which includes DNA having at least a 90% identity to the DNA of one of FIGS.  2 -20 (SEQ ID NO:2, 4, 6, 8, 9, 11-24);    (c) a polynucleotide which hybridizes to the polynucleotide of (a) and which has at least a 70% identity thereto; and    (d) a polynucleotide encoding the same mature polypeptide as a human gene having a coding portion which includes DNA having at least a 90% identity to a DNA included in the deposited clone.    
     
     
         2 . The polynucleotide of  claim 1  wherein the human gene includes DNA contained in the deposited clone.  
     
     
         3 . The polynucleotide of  claim 1  wherein the member is a polynucleotide encoding the same polypeptide as the polynucleotide of  FIG. 1  (SEQ ID NO:1).  
     
     
         4 . A vector containing the polynucleotide of  claim 1 .  
     
     
         5 . A host cell transformed or transfected with the vector of  claim 4 .  
     
     
         6 . A process for producing cells capable of expressing a polypeptide comprising genetically engineering cells with the vector of  claim 4 .  
     
     
         7 . A process for producing a polypeptide comprising: expressing from the host cell of  claim 5  the polypeptide encoded by said polynucleotide.  
     
     
         8 . A polypeptide comprising a member selected from the group consisting of: (i) a polypeptide encoded by a human gene, said human gene having a coding portion whose DNA has at least a 90% identity to the DNA of one of  FIGS. 2-20  (SEQ ID NO:2, 4, 6, 8, 9, 11-24); (ii) a polypeptide encoded by the polynucleotide of  FIG. 1  (SEQ ID NO: 1) and fragments, analogs and derivatives thereof; and (iii) a polypeptide encoded by the human gene whose coding region includes a DNA having at least a 90% identity to the DNA contained in the deposited clone and fragments, analogs and derivatives of said polypeptide.  
     
     
         9 . The polypeptide of  claim 8  wherein the polypeptide is encoded by the polynucleotide having a sequence as set forth in  FIG. 1  (SEQ ID NO: 1).  
     
     
         10 . An antibody against the polypeptide of  claim 8 .  
     
     
         11 . A compound which inhibits activation of the polypeptide of  claim 8 .  
     
     
         12 . A method for the treatment of a patient having need to inhibit a breast specific gene protein comprising: administering to the patient a therapeutically effective amount of the compound of  claim 11 .  
     
     
         13 . The method of  claim 12  wherein the compound is a polypeptide and the therapeutically effective amount of the compound is administered by providing to the patient DNA encoding said polypeptide and expressing said polypeptide in vivo.  
     
     
         14 . A method for the treatment of a patient having need of a breast specific gene protein comprising: administering to the patient a therapeutically effective amount of the polypeptide of  claim 8 .  
     
     
         15 . A process for diagnosing a disorder of the breast in a host comprising: 
 determining transcription of a human gene in a sample derived from non-breast tissue of a host, said gene having a coding portion which includes DNA having at least 90% identity to DNA selected from the group consisting of the DNA of  FIGS. 1-20  (SEQ ID NO:2, 4, 6, 8, 9, 11-24), whereby said transcription indicates a disorder of the breast in the host.    
     
     
         16 . The process of  claim 15  wherein transcription is determined by detecting the presence of an altered level of RNA transcribed from said human gene.  
     
     
         17 . The process of  claim 15  wherein transcription is determined by detecting the presence of an altered level of DNA complementary to the RNA transcribed from said human gene.  
     
     
         18 . The process of  claim 15  wherein transcription is determined by detecting the presence of an altered level of an expression product of said human gene.  
     
     
         19 . A process for determining a disorder of a breast in a host comprising: 
 contacting the antibody of  claim 10  to a fluid sample derived from a host;    determining the presence of an altered level of a BSG gene product in said sample.    
     
     
         20 . A process for identifying antagonists to the polypeptide of  claim 8  comprising: 
 contacting said polypeptide with a natural substrate and a labeled compound to be screened either simultaneously or in either consecutive order; and    determining whether the therapeutic effectively competes with the natural substrate in a manner sufficient to prevent binding of the protein to its substrate.