Nr-cam gene, nucleic acids and nucleic acid products for therapeutic and diagnostic uses for tumors

Abstract

The present invention relates to the identification of a novel role of Nr-CAM in cell transformation and aberrant cellular proliferation. In particular, the present invention relates to the altered gene expression of Nr-CAM in a number of primary tumors and cell lines derived from tumors, in addition to, the altered gene expression of ligands for Nr-CAM. Further, the present invention relates, in part, to the Applicants' surprising discovery that the inhibition of Nr-CAM gene expression or the inhibition of Nr-CAM activity in transformed cells reverses the transformed phenotype.

1 . A composition for the inhibition of tumorigenesis comprising a pharmaceutical carrier and an antisense nucleic acid comprising at least 100 nucleotides hybridizable in a cell to at least a portion of an RNA transcript of a Nr-CAM gene of SEQ ID NO: 1 in an amount effective to inhibit tumorigenesis by inhibiting hyperproliferation of a human tumor cell having high Nr-CAM expression.  
     
     
         2 . (canceled)  
     
     
         3 . A method of inhibiting proliferation of a human tumor cell overexpressing Nr-CAM in a subject comprising administering locally to the subject an effective amount of a Nr-CAM antisense nucleic acid comprising the complement of nucleotides 119 to 1434 of SEQ. ID. NO.: 1; wherein the tumor cell comprises a glioblastoma, a glioma, an astrocytoma, or an oligodendroglioma.  
     
     
         4 - 5 . (canceled)  
     
     
         6 . The method according to  claim 3  in which the subject is a human.  
     
     
         7 . (canceled)  
     
     
         8 . The method according to  claim 3  in which the glioblastoma is glioblastoma multiforme.  
     
     
         9 - 21 . (canceled)  
     
     
         22 . The composition of  claim 1 , wherein the composition is formulated as a liquid.  
     
     
         23 . (canceled)  
     
     
         24 . The method of  claim 3 , wherein the local administration is by direct injection.  
     
     
         25 . The method of  claim 24 , wherein the Nr-CAM antisense nucleic acid is administered locally by direct injection at the site or former site of the tumor.  
     
     
         26 . The method of  claim 25 , wherein the administration is intratumoral.  
     
     
         27 - 30 . (canceled)  
     
     
         31 . An isolated nucleic acid comprising at least 100 nucleotides, the isolated nucleic acid hybridizable, under highly stringent conditions comprising hybridization in an aqueous solution containing 6×SSC at 65° C., to at least a portion of a messenger RNA having SEQ ID NO: 1 and encoding human Nr-CAM, wherein the oligonucleotide inhibits the expression of Nr-CAM in a tumor cell.  
     
     
         32 - 33 . (canceled)  
     
     
         34 . The composition of  claim 1 , wherein the antisense nucleic acid comprises the complement of nucleotides 119 to 1434 of SEQ ID NO: 1.  
     
     
         35 . The composition of  claim 1 , wherein the antisense nucleic acid comprises the complement of nucleotides 1410 to 2746 of SEQ ID NO: 1.