Detection of pkc-iota as a biomarker for brain tumorigenesis

Abstract

A method of detecting brain tumorigenesis in a subject, the method including the steps of (a) obtaining a sample from the brain of the human subject, (b) detecting quantitatively or semi-quantitatively in the sample a level of expression for PKC-iota and (c) comparing the expression level in (b) to a level of expression in a normal control, wherein overexpression of PKC-iota, with respect to the control, indicates the presence of a glioma or meningioma in the subject. The present invention is based upon the discovery that PKC-iota levels are elevated during brain tumorigenesis. Furthermore, the proliferation rate of the tumor correlates with the level of PKC-iota. The invention also provides methods of treating gliomas and meningiomas by administering to the subject a compound that inhibits the expression of PKC-iota. The compound can be a small interfering RNA (siRNA) molecule.

1 . A method of diagnosing the presence of a glioma or meningioma in a subject, comprising:
 (a) obtaining a sample from the brain of the human subject;   (b) detecting quantitatively or semi-quantitatively in the sample a level of expression for PKC-iota protein or PKC-iota-specific mRNA; and   (c) comparing the expression level in (b) to a level of expression in a normal control, wherein overexpression of PKC-iota protein or PKC-iota-specific mRNA, with respect to the control, indicates the presence of glioma or meningioma in the subject.   
     
     
         2 . The method according to  claim 1  wherein the step of detecting detects the quantitative level of expression of PKC-iota in a sample tissue wherein the relative level of expression of PKC-iota in the sample as compared to the control correlates with the proliferation rate of the tumor. 
     
     
         3 . A diagnostic kit for the detection of brain tumorigenesis comprising in combination:
 an anti-PKC-iota antibody;   a labeled secondary antibody capable of immunocomplexing with the anti-PKC-iota antibody;   a positive control derived from a tissue sample of a brain tumor; and   a negative control derived from a normal brain tissue sample.   
     
     
         4 . The diagnostic kit according to  claim 3  further comprising a suitable diluent for the brain tissue sample to be tested. 
     
     
         5 . The diagnostic kit according to  claim 3  wherein the label of the secondary antibody is selected from the group consisting of a fluorescent label, an enzyme label and a radioactive label. 
     
     
         6 . A method of treating a brain tumor in a subject comprising the step of administering to the subject a compound that inhibits the expression of PKC-iota. 
     
     
         7 . The method according to  claim 6  wherein the compound is a small interfering RNA molecule. 
     
     
         8 . The method according to  claim 7  wherein a strand of the siRNA comprises a sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3. 
     
     
         9 . A method of inhibiting expression of human PKC-iota mRNA comprising administering to a subject an effective amount of an siRNA comprising a sense RNA strand and an antisense RNA strand, wherein the sense and an antisense RNA strands form an RNA duplex, and wherein the sense RNA strand comprises a nucleotide sequence substantially identical to a target sequence of about 19 to about 25 contiguous nucleotides in human PKC-iota mRNA such that the human PKC-iota mRNA is degraded. 
     
     
         10 . The method of  claim 9 , wherein the siRNA is administered in conjunction with a delivery reagent. 
     
     
         11 . The method of  claim 10 , wherein the delivery agent is selected from the group consisting of lipofectin, lipofectamine, cellfectin, polycations, and liposomes. 
     
     
         12 . The method of  claim 10 , wherein the delivery agent is a liposome. 
     
     
         13 . The method of  claim 10  wherein the subject is being treated for a glioma or meningioma.