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
References
Jan 1, 1992·Antisense Research and Development·M Kashani-SabetJ G Moreno
Aug 15, 1992·Gene·M KoizumiE Ohtsuka
Feb 1, 1991·Trends in Genetics : TIG·A Gutman, B Wasylyk
Jun 1, 1990·Cell·E R Fearon, B Vogelstein
Aug 1, 1989·Molecular and Cellular Biology·P Sassone-CorsiI M Verma
May 3, 1987·Nature·J L BosB Vogelstein
Feb 1, 1996·Molecular and Cellular Biology·B S YangM C Ostrowski
Jun 14, 1996·Cell·M MuzioV M Dixit
Apr 1, 1996·Current Opinion in Cell Biology·C J Marshall
Apr 1, 1997·Current Biology : CB·J Downward
Jun 6, 1998·Proceedings of the National Academy of Sciences of the United States of America·J M JürgensmeierJ C Reed
Oct 9, 1998·The Journal of Biological Chemistry·H R StennickeG S Salvesen
Jun 2, 2000·Gastroenterology·N ArberZ Halpern
Mar 30, 2001·The Journal of Biological Chemistry·J W SohI B Weinstein
Jul 19, 2001·Journal of the National Cancer Institute·A A Adjei
Jul 27, 2002·Annual Review of Genomics and Human Genetics·William M Grady, Sanford D Markowitz
Citations
Oct 27, 2012·Cancer Gene Therapy·V LisianskyS Kraus
Mar 5, 2010·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Ladan Teimoori-ToolabiSirous Zeinali
Dec 7, 2006·Cancer·Hadas Dvory-SobolNadir Arber
Mar 4, 2009·Biochemical and Biophysical Research Communications·Phillip J WilderAngie Rizzino
Jun 9, 2016·PloS One·Shiran ShapiraNadir Arber
Apr 27, 2017·Oncotarget·Shiran ShapiraNadir Arber
May 18, 2016·Open Forum Infectious Diseases·Bart FeveryOliver Lenz
Nov 24, 2006·Molecular Cancer Therapeutics·Hadas Dvory-SobolNadir Arber
Jun 27, 2021·Oncogene·Shiran ShapiraNadir Arber