Expression analysis of FKBP54 in the diagnosis and treatment of prostate cancer

Abstract

The invention relates to compositions, kits, and methods for detecting, characterizing, preventing, and treating prostate cancer. FKBP markers are provided, wherein changes in the levels of expression of one or more of the FKBP markers is correlated with the presence of prostate cancer.

1 . A method for identifying a compound that is a candidate compound for treating prostate cancer, comprising:
 measuring the expression of FKBP54 in a biological sample exposed to a test compound; and   comparing the expression of FKBP54 in the sample exposed to a test compound to a baseline value, whereby the test compound can be identified as a candidate compound for treating prostate cancer when the expression level of FKBP54 in the presence of the test compound is less than the baseline value.   
     
     
         2 . The method of  claim 1 , wherein the method further comprises obtaining the baseline value by measuring the expression level of FKBP54 in a biological sample in the absence of the test compound. 
     
     
         3 . The method of  claim 1 , wherein the step of measuring the expression of FKBP54 further comprises measuring the amount of at least one of FKBP54 polypeptide, FKBP54 mRNA, and FKBP54 cDNA. 
     
     
         4 . The method of  claim 3  wherein the step of measuring the amount of FKBP54 polypeptide comprises contacting the biological sample with an antibody that specifically binds to the FKBP54 polypeptide. 
     
     
         5 . The method of  claim 1 , wherein the biological sample contains at least one of polypeptides, mRNA, and cDNA from prostate cancer cells. 
     
     
         6 . The method of  claim 1 , wherein the biological sample comprises polypeptides from prostate cancer cells. 
     
     
         7 . The method of  claim 1 , wherein the biological sample comprises at least one of polypeptides, mRNA, and cDNA from a prostate cancer cell line. 
     
     
         8 . The method of  claim 1 , wherein the biological sample comprises at least one of polypeptides, mRNA, and cDNA from a sample of a prostate cancer tumor. 
     
     
         9 . The method of  claim 1 , wherein the test compound is selected from a chemical library. 
     
     
         10 . The method  claim 1 , wherein said test compound is selected from the group consisting of small molecules, peptides, and nucleic acid molecules. 
     
     
         11 . The method of  claim 1 , wherein the test compound is an antisense oligonucleotide complementary to a polynucleotide corresponding to a FKBP54 marker. 
     
     
         12 . A method for assaying a sample of a subject for an indicator of prostate cancer, the method comprising: obtaining a biological sample from the subject; determining the level of FKBP54 in the sample; comparing the level of the marker in the sample to a baseline value, wherein a difference in the level of FKBP54 determined in the sample, when compared to the baseline value, comprises an indicator of the presence of prostate cancer in the subject. 
     
     
         13 . The method of  claim 12 , wherein the biological sample comprises prostate cells. 
     
     
         14 . The method of  claim 12 , wherein the biological sample comprises a body fluid. 
     
     
         15 . The method of  claim 14 , wherein the body fluid is selected from the group consisting of blood, serum, plasma, urine, and saliva. 
     
     
         16 . The method of  claim 12 , wherein the level of FKBP54 in the sample is assessed by detecting the presence of FKBP54 polypeptide or portion thereof. 
     
     
         17 . The method of  claim 12 , wherein the level of FKBP54 in the sample is assessed by detecting the presence in the sample of a transcribed polynucleotide or portion thereof. 
     
     
         18 . The method of  claim 17 , wherein the transcribed polynucleotide is selected from the group consisting of mRNA and cDNA. 
     
     
         19 . The method of  claim 12 , wherein the baseline value is the level of FKBP54 in at least one sample from a normal subject. 
     
     
         20 - 26 . (canceled) 
     
     
         27 . A method of assessing the potential of a test compound to trigger prostate cancer in a cell, the method comprising:
 a) maintaining separate aliquots of cells in the presence and absence of the test compound; and   b) comparing expression of a FKBP54 marker in each of the aliquots, wherein a significantly enhanced level of expression of the FKBP54 marker in the aliquot maintained in the presence of the test compound, relative to the aliquot maintained in the absence of the test compound, is an indication that the test compound possesses the potential for triggering prostate cancer in a cell.   
     
     
         28 . A method of treating a subject afflicted with prostate cancer, the method comprising providing to cells of the subject an antisense oligonucleotide complementary to a polynucleotide corresponding to a FKBP54 marker. 
     
     
         29 . A method of inhibiting prostate cancer in a subject at risk for developing prostate cancer, the method comprising inhibiting expression of a gene corresponding to a FKBP54 marker. 
     
     
         30 . A method for identifying a compound useful for treating prostate cancer, comprising:
 a) measuring the expression level of a FKBP54 marker in a cell in the presence of a test compound; and   b) comparing the expression measured in step a) to the expression of a FKBP54 marker in a cell in the absence of the compound, wherein the compound is useful for treating prostate cancer when the expression level of the FKBP54 marker in the presence of the test compound is lower than its expression level in the absence of the test compound.   
     
     
         31 . The method of  claim 30 , wherein the expression level is determined by measuring the levels of mRNA of the FKBP54 marker. 
     
     
         32 . The method of  claim 30 , wherein the expression level is determined by measuring the levels of the protein of the FKBP54 marker. 
     
     
         33 . The method of  claim 30 , wherein the cell is a prostate cancer cell. 
     
     
         34 . A method of treating prostate cancer in a patient, comprising administering to the patient a compound which decreases the expression of a FKBP54 marker. 
     
     
         35 . The method of  claim 34 , wherein the compound decreases expression of mRNA of the FKBP54 marker. 
     
     
         36 . The method of  claim 34 , wherein the compound decreases expression of the FKBP54 marker protein. 
     
     
         37 . A method of assessing the efficacy of a test compound for inhibiting prostate cancer in a subject, the method comprising:
 obtaining a first biological sample from the subject;   obtaining a second biological sample from the subject;   exposing the first sample to the test compound;   determining the levels of expression of FKBP54 in the first and second samples; and   comparing the levels expression of FKBP54 in the samples, wherein a lower level of expression of FKBP54 in the first sample, relative to the second sample, is an indication that the test compound is efficacious for inhibiting prostate cancer in the subject.   
     
     
         38 . The method of  claim 37 , wherein the first and second samples are portions of a single sample obtained from the subject. 
     
     
         39 . The method of  claim 37 , wherein the first and second samples are portions of pooled samples obtained from the subject. 
     
     
         40 . The method of  claim 37 , wherein one or both of the samples comprise cells from the subject. 
     
     
         41 . The method of  claim 40 , wherein the cells are collected from the prostate gland. 
     
     
         42 . The method of  claim 40 , wherein the cells are collected from blood. 
     
     
         43 . The method of  claim 37 , wherein the levels of FKBP54 are determined by measuring the amount of FKBP54 polypeptide in the samples. 
     
     
         44 . The method of  claim 43 , wherein the amount of polypeptide in the samples is measured using a reagent that specifically binds to the FKBP54 polypeptide. 
     
     
         45 . The method of  claim 44 , wherein the reagent is selected from the group consisting of an antibody, an antibody derivative, and an antibody fragment. 
     
     
         46 . The method of  claim 37 , wherein the levels of FKBP54 are determined by detecting the amount of a transcribed polynucleotide or portion thereof. 
     
     
         47 . The method of  claim 46 , wherein the transcribed polynucleotide is an mRNA. 
     
     
         48 . The method of  claim 46 , wherein the transcribed polynucleotide is a cDNA. 
     
     
         49 . The method of  claim 46 , wherein the detecting further comprises amplifying the transcribed polynucleotide or portion thereof. 
     
     
         50 . The method of  claim 46 , wherein the detecting further comprises amplifying the transcribed polynucleotide or portion thereof. 
     
     
         51 . The method of  claim 37 , wherein the levels of expression in the first and second samples differs by a factor of at least about 2. 
     
     
         52 . The method of  claim 37 , wherein the levels of expression in the first and second samples differs by a factor of at least about 3. 
     
     
         53 . The method of  claim 37 , wherein the subject is a human. 
     
     
         54 . The method of  claim 37 , further comprising repeating the method using a plurality of different test compounds.