Reversal Of The Malignant Phenotype Of Bladder Tumor Cells By A C-myc Specific Ribozyme

Advances in the understanding of the molecular genetics of cancer cells have brought about the concept of oncogenes. c-myc is a protooncogene whose normal primary effect is related to the stimulation of cell growth and differentiation. It's amplification and overexpression have been observed in a wide variety of human leukemia and solid tumors, including bladder tumor. c-myc amplification, overexpression or both of them appears to be responsible for the malignant transformation of the cells. Blockage of c-myc expression with c-myc antisense oligonucleotides and antisense RNA have confirmed that c-myc is crucial for cell proliferation. Down-regulation of c-myc expression is associated with apoptotic cell death. Hence, reducing the level of c-myc mRNA translation in cancer cells may be effective in inducing differentiation and reversal of malignancy.Ribozymes are catalytic RNAs that can cleave specific RNA sequences only requiring the presence of divalent metal ions at neutral or higher pH. The so-called hammerhead ribozymes contain a conserved region of 24 nucleotides which has to be flanked at both the 5' and the 3' ends by sequences that are at least 8 nucleotides long and complementary to the target sequence surrounding the cleavage site. Transacting catalytic RNAs use any GUN(where N is A, C, or U) as the target for cleavage of the RNA. Specificity of the cleavage reaction is achieved by complementarity between the ribozyme and the sequences flanking the target RNA.