Identification of a pin specific gene and protein (pin-1) useful as a diagnostic treatment for prostate cancer

Abstract

The invention relates to nucleic acids encoding a mammalian ABCA5 gene, and proteins encoded thereby, whose expression is increased in certain diseases, disorders, or conditions, including, but not limited to, PIN. Further, the invention relates to diagnostic assays for identifying the DNA-binding protein ABCA5 (also known as PIN-1). The invention also relates to oligonucleotide sequence(s) or antibodies that specifically bind with ABCA5 or variants thereof.

1 . An isolated nucleic acid sequence comprising SEQ ID NO:3, wherein said isolated nucleic acid sequence specifically binds with a mammalian ABCA5 polypeptide or fragment thereof. 
     
     
         2 . The isolated nucleic acid sequence of  claim 1 , wherein said isolated nucleic acid consists of SEQ ID NO:3. 
     
     
         3 . The isolated nucleic acid sequence of  claim 1 , wherein said isolated nucleic acid is a variant of SEQ ID NO:3, wherein said variant is the same length as SEQ ID NO:3, further wherein said variant has the biological activity of SEQ ID NO:3. 
     
     
         4 . The isolated nucleic acid sequence of  claim 1 , wherein said isolated nucleic acid is a derivative of SEQ ID NO:3, wherein said derivative is at least one nucleic acid residue shorter than SEQ ID NO:3, further wherein said derivative has the biological activity of SEQ ID NO:3. 
     
     
         5 . A vector comprising the nucleic acid of  claim 1 . 
     
     
         6 . An isolated nucleic acid complementary to the nucleic acid of  claim 1 . 
     
     
         7 . An isolated antibody that specifically binds with a mammalian ABCA5 polypeptide or a fragment thereof. 
     
     
         8 . The antibody of  claim 7 , wherein said antibody is selected from the group consisting of a polyclonal antibody, a monoclonal antibody, a humanized antibody, a chimeric antibody, and a synthetic antibody. 
     
     
         9 . The antibody of  claim 7 , wherein said ABCA5 polypeptide is a recombinant polypeptide or a native polypeptide. 
     
     
         10 . A method of diagnosing PIN in a mammal, said method comprising:
 a. obtaining a biological sample from said mammal;   b. determining the level of ABCA5 in said biological sample;   c. comparing the level of ABCA5 in said biological sample with the level of ABCA5 in a biological sample obtained from a like mammal not afflicted with PIN,   wherein a higher level of ABCA5 in said biological sample from said mammal compared with the level of ABCA5 in said biological sample from said like mammal is an indication that said mammal is afflicted with PIN.   
     
     
         11 . (canceled) 
     
     
         12 . A method of diagnosing a pre-PCA condition in a mammal, said method comprising:
 a. obtaining a biological sample from said mammal;   b. determining the level of ABCA5 in said biological sample;   c. comparing the level of ABCA5 in said biological sample with the level of ABCA5 in a biological sample obtained from a like mammal not afflicted with PIN,   wherein a higher level of ABCA5 in said biological sample from said mammal compared with the level of ABCA5 in said biological sample from said like mammal is an indication that said mammal has a pre-PCA condition.   
     
     
         13 . The method of  claim 10 , wherein said mammal is a human. 
     
     
         14 . The method of  claim 10 , wherein said biological sample is selected from the group consisting of a blood sample, a urine sample, a sputum sample, a peritoneal cavity fluid sample, a perineal cavity fluid sample, a pleural cavity fluid sample, a semen sample, a prostatic fluid sample, stool sample and a bone marrow sample. 
     
     
         15 . The method of  claim 10 , wherein said biological sample is selected from the group consisting of a prostate tissue sample, a seminal vesicle tissue sample, a kidney tissue sample, a liver tissue sample, and a testis tissue sample. 
     
     
         16 . The method of  claim 10 , wherein said determining said presence or level of ABCA5 in said biological sample is conducted by a method selected from the group consisting of a DNA binding EMSA assay, ELISA, RT-PCR, Northern blot, Western blot and in situ hybridization. 
     
     
         17 . The method of  claim 16 , wherein said DNA binding EMSA assay or ELISA is performed with at least one reagent selected from the group consisting of a nucleic acid comprising SEQ ID NO:3 and an antibody which specifically binds ABCA5. 
     
     
         18 . A method of assessing the effectiveness of a treatment for PIN for prevention of prostate cancer in a mammal, said method comprising:
 a. assessing the level of an ABCA5 molecule in said mammal before administration of a treatment for PIN to said mammal; and   b. assessing the level of an ABCA5 molecule in said mammal during or after administration of a treatment for PIN to said mammal;   wherein a different level of said ABCA5 molecule in said mammal during or after administration of said treatment for PIN than said level of said ABCA5 molecule in said mammal before administration of said treatment for PIN is an indication of the effectiveness of said treatment for PIN in said mammal.   
     
     
         19 . The method of  claim 18 , wherein said PIN is HGPIN. 
     
     
         20 . A method of assessing the effectiveness of a treatment for PIN for prevention of a prostate cancer-associated disease or condition in a mammal, said method comprising:
 a. assessing the level of an ABCA5 molecule in said mammal before administration of a treatment for PIN to said mammal; and   b. assessing the level of an ABCA5 molecule in said mammal during or after administration of a treatment for PIN to said mammal;   wherein a different level of said ABCA5 molecule in said mammal during or after administration of said treatment for PIN than said level of said ABCA5 molecule in said mammal before administration of said treatment for PIN is an indication of the effectiveness of said treatment for PIN in said mammal.   
     
     
         21 . The method of  claim 20 , wherein said treatment for PIN is selected from the group consisting of chemotherapy, radiation therapy and surgery. 
     
     
         22 . The method of  claim 20 , wherein said ABCA5 level is assessed by a method selected from the group consisting of a DNA binding assay, RT-PCR, Northern blot, ELISA, Western blot and in situ hybridization. 
     
     
         23 . A method of identifying a compound that reduces expression of an ABCA5 molecule in a cell, said method comprising contacting a cell with a test compound and comparing a level of the ABCA5 molecule expression in said cell with a level of an ABCA5 molecule expression in an otherwise identical cell not contacted with said test compound, wherein a higher or lower level of ABCA5 molecule expression in said cell contacted with said test compound compared with the level of ABCA5 molecule expression in said otherwise identical cell not contacted with said test compound is an indication that said test compound reduces expression of said ABCA5 molecule in a cell, thereby identifying a compound that reduces expression of said ABCA5 molecule in a cell. 
     
     
         24 . A method of treating HGPIN in a mammal, said method comprising administering to said mammal a molecule that inhibits ABCA5 activity in a cell, thereby treating HGPIN in a mammal. 
     
     
         25 . The method of  claim 23 , wherein said molecule is selected from the group consisting of a nucleic acid comprising SEQ ID NO:3, a variant of SEQ ID NO:3, a derivative of SEQ ID NO:3, and SEQ ID NO:3. 
     
     
         26 . A method of treating HGPIN in a mammal, said method comprising administering to said mammal a molecule identified according to the method of  claim 15 , thereby treating HGPIN in a mammal. 
     
     
         27 . A compound identified by the method of  claim 23 . 
     
     
         28 . The compound of  claim 27 , wherein said compound is an antibody or an antisense nucleic acid. 
     
     
         29 . A kit for diagnosing PIN in a sample obtained from a mammal, said kit comprising a molecule that specifically binds with ABCA5 polypeptide or with a nucleic acid encoding a ABCA5 protein, said kit further comprising an applicator, and an instructional material for the use thereof. 
     
     
         30 . The kit according to  claim 29 , wherein said PIN is HGPIN. 
     
     
         31 . The kit of  claim 29 , wherein said molecule that specifically binds with an ABCA5 polypeptide is an antibody or a nucleic acid. 
     
     
         32 . The kit of  claim 29 , wherein said nucleic acid comprises SEQ ID NO:3. 
     
     
         33 . A kit for treating PIN, said kit comprising a compound that inhibits the expression of ABCA5 and an instructional manual for the use thereof. 
     
     
         34 . The kit of  claim 33 , wherein said compound is an antibody or nucleic acid. 
     
     
         35 . The kit of  claim 34 , wherein said nucleic acid comprises SEQ ID NO:3. 
     
     
         36 . The kit of  claim 34 , wherein said nucleic acid is an antisense nucleic acid.