14094, a novel human trypsin family member and uses thereof

Abstract

The invention provides isolated nucleic acids molecules, designated 14094 nucleic acid molecules, which encode a novel trypsin family member. Elevated expression of 14094 mRNA was detected in breast, ovarian, lung, and liver cancers compared to normal cells derived from these tissues. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 14094 nucleic acid molecules, host cells into which the expression vectors have been introduced, and nonhuman transgenic animals in which a 14094 gene has been introduced or disrupted. The invention still further provides isolated 14094 proteins, fusion proteins, antigenic peptides and anti-14094 antibodies. Therapeutic and diagnostic methods utilizing compositions of the invention to, for example, treat, prevent, and/or diagnose neoplastic conditions, are also provided.

1 . A method for identifying a candidate compound capable of modulating the activity of a polypeptide selected from the group consisting of: 
 i) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3;    ii) a polypeptide comprising an amino acid sequence which is at least 95% identical to the amino acid sequence of SEQ ID NO:2;    iii) a polypeptide which is encoded the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3; and    iv) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    the method comprising:    a) contacting a sample comprising the polypeptide with a test compound; and    b) determining the effect of the test compound on the activity of the polypeptide thereby identifying a candidate compound capable of modulating the activity of the polypeptide.    
     
     
         2 . The method of  claim 1 , wherein the sample is an isolated polypeptide, a membrane-bound form of an isolated polypeptide or a cell comprising the polypeptide.  
     
     
         3 . The method of  claim 2 , wherein the cell is a mammalian cell.  
     
     
         4 . The method of  claim 1 , wherein the candidate compound is selected from the group consisting of a peptoid, a peptidomimetic, a peptide, a phosphopeptide, an antibody, an organic molecule, and an inorganic molecule.  
     
     
         5 . The method of  claim 1 , wherein the candidate compound is a member of a biological library.  
     
     
         6 . The method of  claim 1 , wherein the candidate compound is detectably labeled.  
     
     
         7 . The method of  claim 6 , wherein the label is selected from the group consisting of enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials and radioactive materials.  
     
     
         8 . The method of  claim 1 , wherein the candidate compound is attached to a bead.  
     
     
         9 . A method for detecting the presence of a polypeptide selected from the group consisting of: 
 i) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3;    ii) a polypeptide comprising an amino acid sequence which is at least 95% identical to the amino acid sequence of SEQ ID NO:2;    iii) a polypeptide which is encoded the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3; and    iv) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;    the method comprising:    a) contacting the sample with a compound which selectively binds to the polypeptide; and    b) determining whether the compound binds to the polypeptide in the sample.    
     
     
         10 . The method of  claim 9 , wherein the compound which binds to the polypeptide is an antibody.  
     
     
         11 . A method of treating or preventing a disorder characterized by aberrant cellular proliferation or differentiation of a 14094-expressing cell, in a subject, comprising: 
 administering to the subject an effective amount of a compound that modulates the activity or expression of a polypeptide selected from the group consisting of: 
 i) a polypeptide which is encoded by a nucleic acid molecule comprising a nucleotide sequence which is at least 95% identical to a nucleic acid comprising the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3;  
 ii) a polypeptide comprising an amino acid sequence which is at least 95% identical to the amino acid sequence of SEQ ID NO:2;  
 iii) a polypeptide which is encoded the nucleotide sequence of SEQ ID NO:1 or SEQ ID NO:3; and  
 iv) a polypeptide comprising the amino acid sequence of SEQ ID NO:2;  
 such that the aberrant cellular proliferation or differentiation of the 14094-expressing cell is reduced or inhibited.  
   
     
     
         12 . The method of either of  claim 11 , wherein the disorder is a cancer.  
     
     
         13 . The method of  claim 12 , wherein the cancer is selected from the group consisting of a solid tumor, a soft tissue tumor, a metastatic lesion, a sarcoma, a carcinoma, an adenocarcinoma, lung cancer, breast cancer, and colon cancer.  
     
     
         14 . The method of  claim 11 , wherein the compound is selected from the group consisting of a peptide, a phosphopeptide, a small organic molecule, a small inorganic molecule, a vaccine and an antibody.  
     
     
         15 . The method of  claim 11 , wherein the compound is an antibody conjugated to a therapeutic moiety selected from the group consisting of a cytotoxin, a cytotoxic agent and a radioactive metal ion.