Novel, prostate-specific gene for diagnosis, prognosis and management of prostate cancer

Abstract

Disclosed are nucleic acid and amino acid sequences encoded by a novel, prostate specific gene (UC41) and diagnostic techniques for the detection of human prostate cancer utilizing such nucleic acid and amino acid sequences. Genetic probes and methods useful in monitoring the progression and diagnosis of prostate cancer are described. Methods of treatment for prostate cancer utilizing antisense constructs or antibodies specific for UC41 gene products are also described.

What is claimed is:  
     
         1 . An isolated nucleic acid segment comprising a full length sequence or the full length complement of a sequence selected from the group consisting of SEQ ID NO:1, SEQ ID NO:3 and SEQ ID NO:4.  
     
     
         2 . An isolated nucleic acid molecule of a size between about 14 and 100 bases in length, identical in sequence to a contiguous portion of at least 14 bases of a nucleic acid or its complement selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4.  
     
     
         3 . The isolated nucleic acid molecule of  claim 2 , of a size of between about 17 and 100 bases in length.  
     
     
         4 . The isolated nucleic acid molecule of  claim 2 , of a size of between about 20 and 100 bases in length.  
     
     
         5 . The isolated nucleic acid molecule of  claim 2 , of a size of between about 25 and 100 bases in length.  
     
     
         6 . The isolated nucleic acid molecule of  claim 2 , of a size of between about 30 and 100 bases in length.  
     
     
         7 . The isolated nucleic acid according to  claim 1 , wherein the sequence is SEQ ID NO:1.  
     
     
         8 . The isolated nucleic acid according to  claim 1 , wherein the sequence is SEQ ID NO:3.  
     
     
         9 . The isolated nucleic acid according to  claim 1 , wherein the sequence is SEQ ID NO:4.  
     
     
         10 . An isolated nucleic acid encoding a full length amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:5.  
     
     
         11 . An isolated polypeptide comprising a full length amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:5.  
     
     
         12 . An isolated peptide of a size between 10 and 25 amino acids in length, identical in sequence to a contiguous portion of at least 10 amino acid residues of SEQ ID NO:5.  
     
     
         13 . An isolated peptide of a size between 10 and 65 amino acids in length, identical in sequence to a contiguous portion of at least 10 amino acid residues of SEQ ID NO:5.  
     
     
         14 . A method for detecting prostate cancer cells in a biological sample comprising the step of detecting a prostate cancer marker in said sample, wherein said prostate cancer marker is a nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4.  
     
     
         15 . The method of  claim 14 , further comprising the steps of 
 a) amplifying nucleic acids from said sample to form nucleic acid amplification products;    b) contacting said nucleic acid amplification products with an oligonucleotide probe that will hybridize under stringent conditions with said prostate cancer marker;    c) detecting the nucleic acid amplification products which hybridize with said probe; and    d) measuring the amount of said nucleic acid amplification products that hybridize with said probe, 
 wherein an increased amount of said prostate cancer marker in said sample, relative to the amount of said marker in normal tissue samples, is indicative of the prostate cancer cells.  
   
     
     
         16 . The method of  claim 15 , in which said oligonucleotide probe is selected to bind specifically to an isolated nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4.  
     
     
         17 . The method of  claim 14 , further comprising the steps of 
 a) providing primers that will selectively amplify said prostate cancer marker;    b) amplifying said nucleic acids with said primers to form nucleic acid amplification products;    c) detecting said nucleic acid amplification products; and    d) quantifying said nucleic acid amplification products, 
 wherein an increased amount of said prostate cancer marker in said sample, relative to the amount of said marker in normal tissue samples, is indicative of the prostate cancer cells.  
   
     
     
         18 . The method of  claim 17 , wherein said primers are selected to amplify a nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4.  
     
     
         19 . The method of  claim 16 , further comprising determining the prognosis of prostate cancer patients by quantifying the nucleic acid amplification product binding to a probe specific for said prostate cancer marker.  
     
     
         20 . The method of  claim 16 , further comprising determining the diagnosis of human prostate cancer by quantifying the nucleic acid amplification product binding to a probe specific for said prostate cancer marker.  
     
     
         21 . The method of  claim 18 , further comprising determining the prognosis of prostate cancer patients by quantifying the nucleic acid amplification product.  
     
     
         22 . The method of  claim 18 , further comprising determining the diagnosis of human prostate cancer by quantifying the nucleic acid amplification product.  
     
     
         23 . A method of treating individuals with prostate cancer, comprising the steps of: 
 a) obtaining a sample of tissue from an individual with prostate cancer;    b) screening said sample for the expression of a polypeptide comprising SEQ ID NO:2;    c) providing an antibody that reacts immunologically against said polypeptide; and    d) administering an effective amount of said antibody to an individual with prostate cancer.    
     
     
         24 . A method of treating individuals with prostate cancer, comprising the steps of: 
 a) obtaining a sample of tissue from an individual with prostate cancer;    b) screening said sample for the expression of a polynucleotide comprising SEQ ID NO:1;    c) providing an antisense DNA molecule that encodes an RNA molecule that binds to said polynucleotide;    d) providing said antisense DNA molecule in the form of a human vector containing appropriate regulatory elements for the production of said RNA molecule; and    e) administering an effective amount of said vector to an individual with prostate cancer.    
     
     
         25 . A kit for use in detecting prostate cancer cells in a biological sample, comprising: 
 (a) a primer pair for amplifying a nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4; and    (b) containers for each of said primers.    
     
     
         26 . A kit for use in detecting prostate cancer cells in a biological sample, comprising: 
 (a) an oligonucleotide probe which binds under high stringency conditions to an isolated nucleic acid comprising a sequence selected from the group consisting of SEQ ID NO:3 and SEQ ID NO:4; and    (b) a container for said probe.    
     
     
         27 . A kit for use in detecting prostate cancer cells in a biological sample, comprising: 
 (a) an antibody which binds immunologically to a polypeptide comprising SEQ ID NO:5; and    (b) a container for said antibody.    
     
     
         28 . A method for detecting prostate cancer cells in biological samples, comprising the following steps: 
 (a) providing an antibody that binds immunologically to a peptide comprising SEQ ID NO:5;    (b) contacting a human tissue sample with said antibody;    (c) separating antibody bound to said tissue sample from unbound antibody; and    (d) detecting the bound antibody.    
     
     
         29 . A kit for use in detecting prostate cancer cells in a biological sample, comprising: 
 (a) an antibody which binds immunologically to a polypeptide comprising an amino acid sequence selected from SEQ ID NO:5; and    (b) a container for said antibody.    
     
     
         30 . A method for treating individuals with prostate cancer, comprising the following steps: 
 (a) selecting a polypeptide comprising a sequence selected from SEQ ID NO:5;    (b) providing an inhibitor designed to bind specifically to said polypeptide; and    (c) administering an effective dosage of said inhibitor to a prostate cancer patient.    
     
     
         31 . The isolated nucleic acid according to  claim 1 , wherein said nucleic acid is incorporated into a human expression vector.  
     
     
         32 . The isolated nucleic acid according to  claim 10 , wherein said nucleic acid is incorporated into a human expression vector.  
     
     
         33 . The method of  claim 24 , wherein said antisense DNA molecule encodes a full length complementary sequence to SEQ ID NO:1.  
     
     
         34 . The method of  claim 23 , wherein said antibody is in the form of a single-chain antibody.  
     
     
         35 . The method of  claim 34 , wherein said administering step comprises providing an expression vector that encodes said single-chain antibody.