Method and Composition for Cancer Diagnosis and Treatment

Abstract

Methods and compositions for inhibiting the onset of cancer, and cancer diagnosis and treatment are provided. The treatment method comprises inhibiting the level or function of transcriptional positive factor 4 (PC4). Also provided are methods of screening for cancer inhibition agents based on inhibition of PC4 expression or function.

1 . A method of diagnosing a tumor comprising providing a biological sample from a patient suspected of containing a cancerous tumor, and determining a level of transcriptional positive cofactor 4 (PC4) in the sample, wherein an elevated PC4 level, as compared to a control sample, indicates presence of a tumor. 
     
     
         2 . The method of  claim 1 , wherein the tumor is malignant. 
     
     
         3 . The method of  claim 1 , wherein the sample is selected from the group consisting of lung, blood, bladder, colon, breast, endometrium, thyroid, small bowel, and ovary. 
     
     
         4 . The method of  claim 1 , further comprising determining a level of DNA topoisomerase I in the sample and comparing the level determined to a level of DNA topoisomerase I in a control sample, wherein an elevated DNA topoisomerase level in the sample as compared to the control sample provides an indication of the presence of the tumor. 
     
     
         5 .- 17 . (canceled) 
     
     
         18 . The method of  claim 1 , wherein the level of PC4 is determined from the amount of PC4 mRNA of the sample. 
     
     
         19 . The method of  claim 18 , wherein the amount of PC4 mRNA in the sample is determined by contacting the sample with a sequence, antibody or antibody fragment that specifically binds to the sequence corresponding to PC4 activation domain position 16-30 or positions 26-40. 
     
     
         20 . The method of  claim 18 , wherein the amount of PC4 mRNA in the sample is determined by PCR analysis. 
     
     
         21 . The method of  claim 20 , wherein the PCR analysis specifically amplifies the sequence corresponding to PC4 wt activation domain positions 16-30 or positions 26-40. 
     
     
         22 . The method of  claim 1 , wherein the level of PC4 is determined from the amount of PC4 protein in the sample. 
     
     
         23 . The method of  claim 22 , wherein the amount of PC4 protein in the sample is determined by contacting the sample with an antibody or antibody fragment that specifically binds to the N-terminal, serine rich domain of wt PC4 protein. 
     
     
         24 . The method of  claim 22 , wherein the amount of PC4 protein in the sample is determined by contacting the sample with an antibody or antibody fragment that specifically binds to PC4 protein that contains a phenylalanine at position 77. 
     
     
         25 . The method of  claim 22 , wherein the amount of PC4 protein in the sample is determined by contacting the sample with an antibody or antibody fragment that specifically binds to PC4 protein that contains wt positions 9-19 or 26-40. 
     
     
         26 . The method of  claim 1 , wherein the level of PC4 of the tissue is repeatedly determined from multiple samples obtained from the same tissue over a period of time during which a cancer treatment is provided to validate the cancer treatment. 
     
     
         27 . The method of  claim 26 , wherein the cancer treatment is selected from the group of chemotherapy, radiation therapy, immunotherapy, combinations thereof. 
     
     
         28 . The method of  claim 26 , wherein a reduction in the level PC4 in the sample over the period of time validates successful cancer treatment. 
     
     
         29 . A method of diagnosing a tumor comprising providing a biological sample from a patient suspected of containing a cancerous tumor, culturing the sample for a period of time, and determining a level of transcriptional positive cofactor 4 (PC4) in the cultured sample, wherein an elevated PC4 level, as compared to a control sample, indicates presence of a tumor. 
     
     
         30 . The method of  claim 29 , wherein the sample is selected from the group consisting of lung, blood, bladder, colon, breast, endometrium, thyroid, small bowel, and ovary. 
     
     
         31 . The method of  claim 29 , wherein the level of PC4 is determined from the amount of PC4 mRNA. 
     
     
         32 . The method of  claim 29 , wherein the level of PC4 is determined from the amount of PC4 protein. 
     
     
         33 . The method of  claim 29 , further comprising determining a level of DNA topoisomerase I in the sample and comparing the level determined to a level of DNA topoisomerase I in a control sample, wherein an elevated DNA topoisomerase level in the sample as compared to the control sample provides an indication of the tumor.