Abstract
The von Hippel-Lindau (VHL) is a known tumor suppressor that binds to alpha-subunits of hypoxia-inducible factors and induces ubiquitin-mediated degradation of the protein in an oxygen-dependent manner. VHL is also involved in the regulation of tumor angiogenesis, glycolysis, cell cycle regulation, and apoptosis. In the present study, we showed that ectopic expression of VHL induces apoptosis in renal cell carcinoma 786-O cells which contain only the mutant VHL, evidenced by TUNEL assay and DAPI staining. Furthermore, biochemical studies indicated that expression of VHL in 786-O cells results in both PARP and CPP32 cleavage, suggesting that VHL-induced apoptosis in 786-O cells is caspase dependent. Moreover, we also observed that apoptosis induced by ectopic VHL expression was associated with up-regulation of p27 as well as Bax, implicating the roles of these two proteins in VHL-induced apoptosis. The up-regulation of p27 and Bax by VHL was specific since we did not detect any changes in the level of other apoptotic factors including Fas and Bcl2 by the expression of VHL. We next examined the effect of VHL expression on the tumor growth of 786-O renal cell carcinoma cells in nude mouse. The results showed that injection of Ad.V...Continue Reading
References
Sep 8, 1995·Science·D R DuanR D Klausner
Feb 15, 1995·JAMA : the Journal of the American Medical Association·W M LinehanB Zbar
Mar 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·A PauseR D Klausner
Nov 5, 1997·The Journal of Biological Chemistry·S PalD Mukhopadhyay
Dec 5, 1998·Journal of the National Cancer Institute·A N RakkarP Seth
Jan 27, 1999·Biochemical and Biophysical Research Communications·M KimP Seth
Apr 20, 1999·Oncogene·M SchreiberF L Graham
Dec 29, 2000·Oncogene·A R SchoenfeldR D Burk
Mar 14, 2001·Trends in Biochemical Sciences·S Smith
Aug 22, 2001·The Journal of Biological Chemistry·P DevarajanR D Burk
Feb 1, 2003·Cancer Cell·Fiona A MackM Celeste Simon
Feb 8, 2003·Current Opinion in Genetics & Development·William Kim, William G Kaelin
Citations
Mar 17, 2010·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·María J Calzada
Jan 6, 2012·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Minoru KobayashiTakashi Murakami
Mar 24, 2009·Oncogene·Y GuoR S Freeman
Jun 24, 2008·The Journal of Biological Chemistry·Monica Feijóo-CuaresmaMaria J Calzada
Mar 10, 2011·PloS One·Yanlai LaiYuzuru Shiio
Mar 4, 2014·PloS One·Robert L SatcherSue-Hwa Lin
Apr 16, 2013·The International Journal of Biochemistry & Cell Biology·Linda GummlichWolfgang Dubiel
Aug 15, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Gianluigi MazzoccoliManlio Vinciguerra
May 26, 2007·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·M J Calzada, L del Peso
Feb 7, 2013·International Journal of Pharmaceutics·Cheng Zhe BaiJong-Sang Park
May 8, 2016·Radiologic Clinics of North America·Krishna Prasad ShanbhogueHersh Chandarana
May 9, 2006·Molecular Cell·Jae-Seok RoeHong-Duk Youn
Dec 10, 2014·PloS One·Boban StanojevicRadan Dzodic
Mar 2, 2011·Oncogene·J-S RoeH-D Youn
Nov 10, 2013·PLoS Genetics·Lee D KappMary C Mullins
Oct 19, 2011·The Journal of Bone and Joint Surgery. American Volume·Changbao ChenQingjun Ma
Oct 2, 2012·Oncology Reports·Jianjun ZhuYao Chen
Aug 25, 2018·Cancer Gene Therapy·Changbao ChenXinlong Ma
Nov 6, 2014·Cancer Research·Sophie CouvéBetty Gardie
Feb 17, 2021·Molecular and Cellular Biochemistry·Narayan Acharya, Kamaleshwar P Singh