Materials and methods for inhibiting wip1

Abstract

Isolated or purified oligonucleotides and isolated or purified morpholino oligomers; a method of detecting cancer or a predisposition to cancer in a mammal, comprising comparing the level of expression of Wip1 in the mammal to a control; a method of treating cancer in a mammal that expresses the same or a higher level of Wip1 as compared to a mammal of the same species that does not have cancer, comprising administering to the mammal a cancer-treating effective amount of a Wip1 inhibitor, a method of screening an oligonucleotide or morpholino oligomer for the ability to inhibit the expression of Wip1; a method of determining the efficacy with which a test oligonucleotide or morpholino oligomer inhibits Wip1 expression; a method of screening a compound for Wip1-inhibiting activity; and a method of determining the efficacy with which a test compound inhibits Wip1.

1 . An isolated or purified oligonucleotide consisting essentially of the nucleotide sequence of SEQ ID NO: 1 or SEQ ID NO: 2.  
     
     
         2 . An isolated or purified morpholino oligomer consisting essentially of the sequence of SEQ ID NO: 1 or SEQ ID NO: 2.  
     
     
         3 . A method of detecting cancer or a predisposition to cancer in a mammal, which method comprises comparing the level of expression of Wip1 in a test sample comprising Wip1 obtained from the mammal to the level of expression of Wip1 in a control sample, wherein a higher level of expression of Wip1 in the test sample as compared to the control sample is indicative of cancer or a predisposition to cancer in the mammal.  
     
     
         4 . The method of  claim 3 , wherein Wip1 is in the form of nucleic acid in the test sample and the control sample.  
     
     
         5 . The method of  claim 3 , wherein Wip1 is in the form of protein in the test sample and the control sample.  
     
     
         6 . The method of  claim 3 , wherein the cancer is breast cancer.  
     
     
         7 . A method of treating cancer in a mammal that expresses the same level or a higher level of Wip1 as compared to a mammal of the same species that does not have cancer, which method comprises administering to the mammal a cancer-treating effective amount of a Wip1 inhibitor, whereupon the mammal is treated for cancer.  
     
     
         8 . The method of  claim 7 , wherein the inhibitor is an oligonucleotide or a morpholino oligomer, either one of which hybridizes to any part of a nucleic acid encoding Wip1.  
     
     
         9 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer comprises at least 18 genetic nitrogenous bases.  
     
     
         10 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer hybridizes to exon 1 of a nucleic acid encoding Wip1.  
     
     
         11 . The method of  claim 10 , wherein the oligonucleotide or morpholino oligomer comprises SEQ ID NO: 1.  
     
     
         12 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer hybridizes to any part of the 5′ untranslated region (UTR) of a nucleic acid encoding Wip1.  
     
     
         13 . The method of  claim 12 , wherein the oligonucleotide or morpholino oligomer comprises SEQ ID NO: 2.  
     
     
         14 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer hybridizes to any part of the 3′ UTR of a nucleic acid encoding Wip1.  
     
     
         15 . The method of  claim 8 , wherein the oligonucleotide comprises at least one modified oligodeoxynucleotide.  
     
     
         16 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer is administered in the form of a liposome.  
     
     
         17 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer is administered in the form of a vector.  
     
     
         18 . The method of  claim 17 , wherein the vector is a plasmid expression vector, a retroviral vector, or an adenoviral vector.  
     
     
         19 . The method of  claim 8 , wherein the cancer is in the form of a tumor and the oligonucleotide or morpholino oligomer is administered peritumorally or intratumorally.  
     
     
         20 . The method of  claim 8 , wherein the oligonucleotide or morpholino oligomer is administered with the carrier ethoxylated polyethylenimine (EPEI).  
     
     
         21 . The method of  claim 7 , wherein the inhibitor is a compound that inhibits Wip1 phosphatase activity.  
     
     
         22 . The method of  claim 21 , wherein the inhibitor is a small molecular weight compound.  
     
     
         23 . The method of  claim 7 , wherein the cancer is breast cancer.  
     
     
         24 . A method of screening an oligonucleotide or morpholino oligomer for the ability to inhibit the expression of Wip1, which method comprises comparing the level of expression of Wip1 in a test sample obtained from Wip1-expressing cells that have been contacted with the oligonucleotide or morpholino oligomer to the level of expression of Wip1 in a control sample obtained from Wip1-expressing cells that have not been contacted with the oligonucleotide or morpholino oligomer, respectively, wherein a lower level of expression of Wip1 in the test sample as compared to the control sample is indicative of the ability of the oligonucleotide or morpholino oligomer to inhibit the expression of Wip1.  
     
     
         25 . The method of  claim 24 , wherein Wip1 is in the form of a nucleic acid in the test sample and the control sample.  
     
     
         26 . The method of  claim 24 , wherein Wip1 is in the form of protein in the test sample and the control sample.  
     
     
         27 . A method of determining the efficacy with which a test oligonucleotide or morpholino oligomer inhibits Wip1 expression, which method comprises comparing the level of expression of Wip1 in a test sample obtained from Wip1-expressing cells that have been contacted with the test oligonucleotide or morpholino oligomer to the level of expression of Wip1 in a control sample obtained from Wip1-expressing cells that have been contacted with an oligonucleotide or morpholino oligomer that is known to inhibit the expression of Wip1, wherein a lower level of expression of Wip1 in the test sample as compared to the control sample is indicative of the test oligonucleotide or morpholino oligomer having a greater efficacy for inhibiting the expression of Wip1 than the known oligonucleotide or morpholino oligomer and wherein a higher level of expression of Wip1 in the test sample as compared to the control sample is indicative of the test oligonucleotide or morpholino oligomer having a lower efficacy for inhibiting the expression of Wip1 than the known oligonucleotide or morpholino oligomer.  
     
     
         28 . The method of any of  claim 27 , wherein Wip1 is in the form of nucleic acid in the test sample and the control sample.  
     
     
         29 . The method of  claim 27 , wherein Wip1 is in the form of protein in the test sample and the control sample.  
     
     
         30 . A method of screening a compound for Wip1-inhibiting activity, which method comprises comparing the level of Wip1 phosphatase activity in a test sample obtained from Wip1-expressing cells that have been contacted with the compound to the level of Wip1 phosphatase activity in a control sample obtained from Wip1-expressing cells that have not been contacted with the compound, wherein a lower level of Wip1 phosphatase activity in the test sample as compared to the control sample is indicative of the ability of the compound to inhibit Wip1.  
     
     
         31 . A method of determining the efficacy with which a test compound inhibits Wip1, which method comprises comparing the level of Wip1 phosphatase activity in a test sample obtained from Wip1-expressing cells that have been contacted with the test compound to the level of Wip1 phosphatase activity in a control sample obtained from Wip1-expressing cells that have been contacted with a compound that is known to inhibit Wip1, wherein a lower level of Wip1 phosphatase activity in the test sample as compared to the control sample is indicative of the test compound having a greater efficacy for inhibiting Wip1 than the known compound and wherein a higher level of Wip1 phosphatase activity in the test sample as compared to the control sample is indicative of the test compound having a lower efficacy for inhibiting Wip1 than the known compound.