PMID: 16507412Mar 2, 2006Paper

Gene targeting approach to selectively kill colon cancer cells, with hyperactive K-Ras pathway

Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie
Hadas Dvory-SobolN Arber

Abstract

Ras mutations are present in approximately 50% of human colorectal tumors. We have previously shown that transfection of a non-tumorigenic rat intestinal epithelial cell line, IEC18, by the K-Ras oncogene (R1 cells), resulted in malignant cell transformation. Utilizing the constantly active Ras signaling pathway to selectively target transformed but not normal cells is a plausible goal. To selectively kill Ras transformed cells by over expressing a lethal gene using a Ras-responsive promoter. IEC18, R1 and a number of colon cancer cell lines were transfected with luciferase (Luc) reporter gene under the control of different Ras-responsive elements. The Ras-responsive promoter Py2 contains two copies of adjacent Ets and AP I binding sites followed by a minimal promoter. Apoptotic genes (bax, caspase-8 and PKG) were cloned into the Py2 plasmids. RI cells co-transfected with expression constructs and a selected vector and then grown for 3 weeks under selection. R1, SW480 and HCT116 with mutated c-K-Ras expressed high level of Luc activity following transfection with the Py2 element. IEC18 cell lines that do not contain this mutation expressed negligible low Luc activity. Following transfection of SW480 and R1 cells with Py2-bax, c...Continue Reading

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Citations

Oct 27, 2012·Cancer Gene Therapy·V LisianskyS Kraus
Mar 5, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ladan Teimoori-ToolabiSirous Zeinali
Mar 4, 2009·Biochemical and Biophysical Research Communications·Phillip J WilderAngie Rizzino
Apr 27, 2017·Oncotarget·Shiran ShapiraNadir Arber
Nov 24, 2006·Molecular Cancer Therapeutics·Hadas Dvory-SobolNadir Arber

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