Copi molecules and uses thereof

Abstract

The invention provides diagnostic, prognostic, and therapeutic uses for detecting COP1 overexpression in a variety of cancers. The methods and uses can further include detecting p53 expression. The invention also provides reagents and kits for use in screening for test compounds that interfere with COP1 and p53 binding.

1 . A method for monitoring the efficacy of a cancer therapy in a subject, the method comprising: providing a sample from the subject; and detecting a COP1 molecule in said sample, wherein a reduction in overexpression of said COP1 molecule relative to a control indicates that the cancer therapy is efficacious. 
     
     
         2 . A method for assessing the prognosis for a subject having a cancer, the method comprising:
 providing a sample from the subject; and   detecting a COP1 molecule in said sample, wherein a reduction in overexpression of said COP1 molecule relative to a control indicates an improved prognosis.   
     
     
         3 . The method of  claim 1  further comprising detecting a p53 molecule in said sample, wherein an increase in p53 expression levels or an increase in p53 activity is indicative of an efficacious cancer therapy. 
     
     
         4 . The method of  claim 3  wherein said p53 molecule is wild type. 
     
     
         5 . The method of  claim 3  wherein said p53 molecule is a human p53 molecule. 
     
     
         6 . The method of  claim 3  wherein said p53 molecule is a p53 polypeptide. 
     
     
         7 . The method of  claim 6  wherein said p53 polypeptide is detected using an antibody that specifically binds said p53 polypeptide. 
     
     
         8 . The method of  claim 6  wherein said p53 polypeptide is detected using immunohistochemistry. 
     
     
         9 . The method of  claim 3  wherein said p53 activity is selected from the group consisting of at least one of inhibition of p53-dependent transactivation, inhibition of p53-induced apoptosis, and reduction of p21 mRNA levels. 
     
     
         10 . The method of  claim 1  wherein said COP1 molecule is human COP1. 
     
     
         11 . The method of  claim 1  wherein said COP1 molecule is a COP1 polypeptide. 
     
     
         12 . The method of  claim 11  wherein said COP1 polypeptide is detected using an antibody that specifically binds said COP1 polypeptide. 
     
     
         13 . The method of  claim 11  wherein said COP1 polypeptide is detected using immunohistochemistry. 
     
     
         14 - 15 . (canceled) 
     
     
         16 . The method of  claim 1  further comprising detecting a p21 molecule in said sample, wherein a decrease in p21 expression levels is indicative of a cancer. 
     
     
         17 . The method of  claim 1  wherein the subject is a human. 
     
     
         18 . The method of  claim 1  wherein the cancer is a wild type p53-expressing cancer. 
     
     
         19 . The method of  claim 1  wherein the cancer is selected from the group consisting of at least one of breast cancer, ovarian cancer, colon cancer, lung cancer, and transitional cell cancer. 
     
     
         20 . The method of  claim 19  wherein said ovarian cancer is selected from at least one of a group consisting of serous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma, and mucinous adenocarcinoma. 
     
     
         21 - 93 . (canceled) 
     
     
         94 . The method of  claim 2  further comprising detecting a p53 molecule in said sample, wherein an increase in p53 expression levels or an increase in p53 activity is indicative of an efficacious cancer therapy or an improved prognosis. 
     
     
         95 . The method of  claim 94  wherein said p53 molecule is wild type. 
     
     
         96 . The method of  claim 94  wherein said p53 molecule is a human p53 molecule. 
     
     
         97 . The method of  claim 94  wherein said p53 molecule is a p53 polypeptide. 
     
     
         98 . The method of  claim 97  wherein said p53 polypeptide is detected using an antibody that specifically binds said p53 polypeptide. 
     
     
         99 . The method of  claim 97  wherein said p53 polypeptide is detected using immunohistochemistry. 
     
     
         100 . The method of  claim 94  wherein said p53 activity is selected from the group consisting of at least one of inhibition of p53-dependent transactivation, inhibition of p53-induced apoptosis, and reduction of p21 mRNA levels. 
     
     
         101 . The method of  claim 2  wherein said COP1 molecule is human COP1. 
     
     
         102 . The method of  claim 2  wherein said COP1 molecule is a COP1 polypeptide. 
     
     
         103 . The method of  claim 102  wherein said COP1 polypeptide is detected using an antibody that specifically binds said COP1 polypeptide. 
     
     
         104 . The method of  claim 102  wherein said COP1 polypeptide is detected using immunohistochemistry. 
     
     
         105 - 106 . (canceled) 
     
     
         107 . The method of  claim 2  further comprising detecting a p21 molecule in said sample, wherein a decrease in p21 expression levels is indicative of a cancer. 
     
     
         108 . The method of  claim 2  wherein the subject is a human. 
     
     
         109 . The method of  claim 2  wherein the cancer is a wild type p53-expressing cancer. 
     
     
         110 . The method of  claim 2  wherein the cancer is selected from the group consisting of at least one of breast cancer, ovarian cancer, colon cancer, lung cancer, and transitional cell cancer. 
     
     
         111 . The method of  claim 110  wherein said ovarian cancer is selected from at least one of a group consisting of serous adenocarcinoma, endometrioid adenocarcinoma, clear cell adenocarcinoma, and mucinous adenocarcinoma.