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Reversion Of The Malignant Phenotype Of Gastric Cancer By C-erbB-2 Specific Ribozyme And Antisense RNA

Posted on:1998-08-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:F BiFull Text:PDF
GTID:1104360185496620Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
The abnormal signal transduction is responsible for the uncontrollable growth of cancer cells which is the most remarkable characteristic of cancer cells. The growth, even the occurrence of cancer might be under control if effective method were taken to resume the normal signal transduction. As more and more people realized the importance of signal transduction, a new concept - antisignaling therapy has appeared in cancer therapy. P185, the product of c-erbB-2 oncogene, is a growth factor receptor with tyrosine kinase activity. It can result in a series of phosphorylation or dephosphorylation of this protein on tyrosine residues in cancer cells after binding to its ligands and the activation of tyrosine kinase. In this way, the P185 regulates the proliferation of cancer cells. It was found that the amplification and overexprssion of c-erbB-2 has a close relation to the occurrence, development, metastasis and prognosis.Ribozyme is a kind of RNA with catalytic activity. As it can cleave the target RNA and can be reused in this process, it is taken as a more effective approach in gene therapy in comparation with antisense gene therapy. Here we are going to probe the effect of c-erbB-2 specific ribozyme and antisense RNA to the malignant phenotype of gastric cancer. The results were shown as follows:1 .Taking the c-erbB-2 mRNA as target RNA, computer analysis indicates that the secondary structures of c-erbB-2 mRNA between nt. 2428 to nt. 2776 and nt. 28207 to nt. 3004 are relatively stable. The two regions are of important biological function and are the ideal attacking regions for ribozymes. Three sites, nt. 2438, nt. 2477 and nt. 2751 on the c-erbB-2 mRNA, were selected as the most ideal cleaving sites for ribozymes.2.Three ribozymes targeting at the above three sites on c-erbB-2 mRNA were designed and were named RZ1, RZ2 and RZ3 respectively. Among them, the RZ1 gene was synthesized and the sequence was proved to be correct by automatic sequencer analysis.
Keywords/Search Tags:c-erbB-2, ribozyme, gastric cancer, gene therapy, antisense
PDF Full Text Request
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