Overexpression of DcR1 and survivin in genetically modified cells with pleiotropic drug resistance

Cancer Letters
Irina A DavidovichVictor V Levenson Chernokhvostov

Abstract

A previously identified set of short cDNA fragments (genetic suppressor elements, GSEs) expressed in human HT1080 cells protects them against several chemotherapeutic drugs. We show here that DNA damaging agent cytosine arabinoside can induce apoptosis in GSE-containing drug-resistant derivatives (M125 cells) of HT1080, suggesting that apoptotic pathways are preserved in M125. We also show that both parental cells and M125 constitutively express Fas ligand and TNF-related apoptosis inducing ligand, thus pre-disposing cells to apoptosis. In both cell lines, induction of apoptosis requires simultaneous treatment with low doses of cycloheximide (CHX) and death ligands, however, drug-resistant M125 are substantially more resistant to this treatment. Expression of survivin and decoy receptor 1 (DcR1) is lower in parental cells and is further decreased by CHX. In resistant M125 cell, both survivin and DcR1 are overexpressed even after CHX treatment, which can explain relative resistance of these cells. Thus, apoptosis remains intact in cells with resistance-inducing GSE, suggesting that apoptosis inhibitors can be targeted by anti-cancer therapy in drug-resistant tumors.

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Citations

Sep 19, 2006·Molecular and Cellular Biology·Delphine MérinoOlivier Micheau
Mar 22, 2014·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·L GottwaldA Jeziorski
May 5, 2012·Gynecologic Oncology·Letícia da Conceição BragaAgnaldo Lopes da Silva-Filho
Sep 28, 2010·Ultrasound in Medicine & Biology·Adrien DaigelerJoerg Hauser
May 4, 2013·British Journal of Pharmacology·O MicheauF Dufour
Jan 27, 2005·Current Problems in Cancer·Monica Mita, Anthony W Tolcher
Jul 22, 2006·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Heike MarxfeldJohannes H Harleman

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