Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences.

Ayesh, Basim and Matouk, I and Ohana, P and Sughayer, M A and Birman, T and Ayesh, S and Schneider, T and de Groot, N and Hochberg, A (2003) Inhibition of tumor growth by DT-A expressed under the control of IGF2 P3 and P4 promoter sequences. Molecular therapy : the journal of the American Society of Gene Therapy, 7 (4). pp. 535-41. ISSN 1525-0016

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Abstract

The human IGF2 P3 and P4 promoters are highly active in a variety of human cancers. We here present an approach for patient oriented therapy of TCC bladder carcinoma by driving the diphtheria toxin A-chain (DT-A) expression under the control of the IGF2 P3 and P4 promoter regulatory sequences. High levels of IGF2 mRNA expression from P3, P4 or both promoters were detected in 18 TCC samples (n = 29) by ISH or RT-PCR. Normal bladder samples (n = 4) showed no expression from either promoter. The activity and specificity of the IGF2 P3 and P4 regulatory sequences were established in human carcinoma cell lines by means of luciferase reporter gene assay. These sequences were used to design DT-A expressing, therapeutic vectors (P3-DT-A and P4-DT-A). The activity of both was determined in cell lines (in vitro) and the activity of P3-DT-A was determined in a heterotopic animal model (in vivo). The treated cell lines highly responded to the treatment in a dose-response manner, and the growth rate of the developed tumors in vivo was highly inhibited (70%) after intratumoraly injection with P3-DT-A compared to non-treated tumors (P < 0.0002) or tumors treated by luciferase gene expressing LucP3 vector (P < 0.002).

Item Type: Article
Subjects: Q Science > QH Natural history > QH301 Biology
Depositing User: د. باسم محمد حسين عايش
Date Deposited: 14 Mar 2018 09:53
Last Modified: 14 Mar 2018 09:53
URI: http://scholar.alaqsa.edu.ps/id/eprint/346

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