Inhibition of MKP-1 expression potentiates JNK related apoptosis in renal cancer cells

The Journal of Urology
R MizunoMasaru Murai

Abstract

Mitogen-activated protein kinases (MAPKs) comprise 3 subgroups, that is extracellular signal-regulated protein kinase, c-Jun N-terminal kinase (JNK) and p38 MAPK (p38). In this study we analyzed the role of JNK as well as the expression of MAPK phosphatase-1 (MKP-1) in renal cancers. Four renal cell carcinoma (RCC) cell lines were used. The effects of anisomycin (JNK activator) and Ro-318220 (MKP-1 expression inhibitor) were analyzed by alamar blue assay. Apoptosis was determined by flow cytometric TUNEL analysis, nuclear morphological alternations and the detection of DNA fragmentation. Changes in MKP-1 expression as well as the activation of extracellular signal-regulated protein kinases and JNK were analyzed by Western blotting. All cell lines treated with anisomycin resulted in a transient activation of JNK without inducing apoptosis. Since we hypothesized that elevated MKP-1 expression could possibly prevent persistent JNK activation, Ro-318220 was used. When cells were treated with Ro-318220, MKP-1 expression decreased in Caki-1 and KU 20-01 cells but not in ACHN or 769P cells. Combined treatment of Caki-1 and KU 20-01 cells with anisomycin and Ro-318220 resulted in a decrease in MKP-1 expression concomitant with persiste...Continue Reading

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Citations

Apr 2, 2008·Current Oncology Reports·Taolin Yi, Daniel Lindner
Mar 19, 2013·Oncogene·J StebbingG Giamas
Jun 17, 2008·The Journal of Urology·Akio HoriguchiMasamichi Hayakawa
Sep 1, 2016·International Journal of Urology : Official Journal of the Japanese Urological Association·Tsukasa Igawa
Aug 23, 2005·Carcinogenesis·Shane P DugganDermot Kelleher
Apr 3, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Yu Jin JungWon Kim
Mar 1, 2015·Molecular and Cellular Biochemistry·Francisco A Aguilar-AlonsoMaría Elena Ibarra-Rubio
May 7, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Federico RojoJoan Albanell
Apr 29, 2021·Computers in Biology and Medicine·Manuel JuradoAntonio Zorzano

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