Mda-7 proteins and methods of use thereof

Abstract

This invention provides a method of generating a subtracted cDNA library of a cell comprising: a) generating a cDNA library of the cell; b) isolating double-stranded DNAs from the cDNA library; c) releasing the double-stranded cDNA inserts from the double-stranded DNAs; d) denaturing the isolated double-stranded cDNA inserts; e) hybridizing the denatured double-stranded cDNA inserts with a labelled single-stranded nucleic acid molecules which are to be subtracted from the cDNA library; and f) separating the hybridized labeled single-stranded nucleic acid molecule from the double-stranded cDNA inserts, thereby generating a subtracted cDNA library of a cell. This invention also provides different uses of the subtracted library.

1 . A method for reversing the malignant phenotype of a malignant cell comprising introducing a nucleic acid comprising the mda-7 gene linked to a regulatory element such that the expression of the mda-7 gene is under the control of the regulatory element into the malignant cell under conditions permitting the expression of the mda-7 gene, whereby the transforming phenotype of the malignant cell is reversed. 
     
     
         2 . A method for inducing growth suppression in a tumorigenic and metastatic cell comprising introducing a nucleic acid comprising the mda-7 gene linked to a regulatory element such that the expression of the mda-7 gene is under the control of the regulatory element into the tumorigenic and metastatic cell, wherein growth suppression is induced. 
     
     
         3 . A method for inducing terminal differentiation in a tumorigenic and metastatic cell comprising introducing a nucleic acid comprising the mda-7 gene linked to a regulatory element such that the expression of the mda-7 gene is under the control of the regulatory element into the tumorigenic and metastatic cell, wherein terminal differentiation is induced. 
     
     
         4 . The method of  claim 1 , wherein the cell is a melanoma cell, a leukemia cell, a lymphoma cell, a neuroblastoma cell, or a glioblastoma multiforme cell. 
     
     
         5 . The method of  claim 1 , wherein the regulatory element is a promoter. 
     
     
         6 . The method of  claim 5 , wherein the promoter is a tissue-specific promoter or an inducible promoter. 
     
     
         7 . The method of  claim 1 , wherein the nucleic acid is introduced into the cell by naked DNA technology, retroviral vectors, antibody-coated liposomes, mechanical or electrical means.