Methods of screening for modulators of cell proliferation and methods of diagnosing cell proliferation states

Abstract

Described herein are methods that can be used for diagnosis and prognosis of cellular proliferation. Also described herein are methods that can be used to screen candidate bioactive agents for the ability to modulate cellular proliferation. Additionally, methods and molecular targets (genes and their products) for therapeutic intervention in cancers are described.

1 - 33 . (canceled) 
     
     
         34 . A method of evaluating a hyper-proliferative disorder comprising:
 (a) determining the level of expression of kindle-like spindle protein (KSP) in a sample from a tissue having the hyper-proliferative disorder; and   (b) comparing said KSP expression level to a standard or control level of expression, wherein an increase indicates that the hyper-proliferative disorder is KSP-mediated.   
     
     
         35 . The method of  claim 34  wherein said hyper-proliferative disorder is cancer. 
     
     
         36 - 59 . (canceled) 
     
     
         60 . The method of  claim 34 , wherein the sample is selected from the group consisting of a blood sample, a urine sample, a buccal sample, a PAP smear, a cerebral spinal fluid sample, a breast tissue sample, a lung tissue sample, and a colon tissue sample. 
     
     
         61 . The method of  claim 34 , wherein the standard or control level is representative of normal cells not in a hyper-proliferative state. 
     
     
         62 . The method of  claim 61 , wherein the hyper-proliferative disorder is cancer, and step (b) is performed by nucleic acid hybridization. 
     
     
         63 . The method of  claim 34 , wherein step (a) further comprises determining the expression level of at least one additional cell proliferation protein; and step (b) comprises the expression levels of each cell proliferation protein with the expression level of the same protein in the standard or control level. 
     
     
         64 . The method of  claim 63 , wherein the additional cell proliferation protein is a kinesin. 
     
     
         65 . The method of  claim 63 , wherein the standard or control level for each cell proliferation protein is representative of normal cells not in a hyper-proliferative state. 
     
     
         66 . The method of  claim 65 , wherein the hyper-proliferative disorder is cancer. 
     
     
         67 . The method of  claim 34 , wherein step (a) comprises determining the amount of nucleic acid encoding KSP in the sample. 
     
     
         68 . The method of  claim 67 , wherein the amount of nucleic acid encoding KSP is determined by nucleic acid hybridization. 
     
     
         69 . The method of  claim 67 , wherein the nucleic acid hybridization is in situ hybridization. 
     
     
         70 . The method of  claim 67 , wherein the nucleic acid is DNA. 
     
     
         71 . The method of  claim 67 , wherein the nucleic acid is RNA. 
     
     
         72 . The method of  claim 34 , wherein step (a) comprises determining the amount of KSP protein in the sample. 
     
     
         73 . The method of  claim 72 , wherein the amount of KSP protein is determined by mass spectroscopy. 
     
     
         74 . The method of  claim 72 , wherein the amount of KSP protein is determined by an immunological method. 
     
     
         75 . The method of  claim 74 , wherein the immunological method is an enzyme-linked immunoassay (ELISA). 
     
     
         76 . The method of  claim 72 , wherein the amount of KSP protein is determined by two-dimensional gel electrophoresis. 
     
     
         77 . The method of  claim 34 , further comprising the step of administering a therapeutically effective amount of a KSP inhibitor, when an increase is detected in step (b). 
     
     
         78 . The method of  claim 77 , wherein the hyper-proliferative disorder is cancer. 
     
     
         79 . The method of  claim 77 , wherein the KSP inhibitor is a small molecule having a molecular weight of between 50 kD and 2000 kD.