Mitochondrial localization of muc1

Abstract

The invention provides methods of identifying and making compounds that inhibit the interaction between MUC1 and either or both of HSP70 and HSP90. Also embraced by the invention are in vivo and in vitro methods of inhibiting such an interaction.

1 - 13 . (canceled) 
     
     
         14 . An in vivo method of inhibiting binding of MUC1 to HSP70 or HSP90 in a cancer cell that expresses MUC1, the method comprising:
 (a) identifying a subject as having a cancer that expresses MUC1 or is suspected to express MUC1; and   (b) administering to the subject a compound or, where the compound is a polypeptide, a nucleic acid comprising a nucleic acid sequence encoding the polypeptide, the nucleic acid sequence being operably linked to a transcriptional regulatory element (TRE), wherein the compound inhibits binding of HSP70 or HSP90 to the cytoplasmic domain of MUC1.   
     
     
         15 . The method of  claim 14 , wherein the compound is a peptide fragment of (a) MUC1, (b) HSP70, or (c) HSP90. 
     
     
         16 . The method of  claim 14 , wherein the compound is a peptide fragment of the cytoplasmic domain of MUC1. 
     
     
         17 . The method of  claim 15 , wherein the peptide fragment comprises all or part of amino acids 46-72 of SEQ ID NO:1. 
     
     
         18 . The method of  claim 15 , wherein the peptide comprises all or part of the substrate binding domain of HSP70 or HSP90. 
     
     
         19 . The method of  claim 14 , wherein the compound is an antibody, or an antibody fragment, that binds to the cytoplasmic domain of MUC1. 
     
     
         20 . The method of  claim 14 , wherein the compound is a small molecule. 
     
     
         21 . The method of  claim 20 , wherein the small molecule comprises a nucleic acid aptamer. 
     
     
         22 . The method of  claim 20 , wherein the small molecule consists of a nucleic acid aptamer. 
     
     
         23 . The method of  claim 14 , wherein the subject is a human subject. 
     
     
         24 . The method of  claim 14 , wherein the cancer cell is a breast cancer cell. 
     
     
         25 . The method of  claim 14 , wherein the cancer cell is selected from the group consisting of a lung cancer, colon cancer, pancreatic cancer, renal cancer, stomach cancer, liver cancer, bone cancer, hematological cancer, neural tissue cancer, melanoma, ovarian cancer, testicular cancer, prostate cancer, cervical cancer, vaginal cancer, or bladder cancer cell. 
     
     
         26 . The method of  claim 21 , wherein the TRE is a DF3 enhancer. 
     
     
         27 . A method of killing a cancer cell, the method comprising before, after, or at the same time as performing the method of  claim 14 , exposing the subject to one or more genotoxic agents. 
     
     
         28 . The method of  claim 27 , wherein the one or more genotoxic agents comprise one or more forms of ionizing radiation. 
     
     
         29 . The method of  claim 27 , wherein the one or more genotoxic agents comprise one or more chemotherapeutic agents. 
     
     
         30 . The method of  claim 29 , wherein the one or more chemotherapeutic agents are selected from the group consisting of cisplatin, carboplatin, procarbazine, mechlorethamine, cyclophosphamide, camptothecin, ifosfamide, melphalan, chlorambucil, bisulfan, nitrosurea, dactinomycin, daunorubicin, doxorubicin, bleomycin, plicomycin, mitomycin, etoposide, verampil, podophyllotoxin, tamoxifen, taxol, transplatinum, 5-fluorouracil, vincristin, vinblastin, methotrexate, and an analog of any of the aforementioned.