Display options
Cite
Doonachar A, Gallo MD, Doukas D, et al. Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines. Cancer Cell Int. 2015;15:23doi: 10.1186/s12935-015-0175-3.
Doonachar, A., Gallo, M. D., Doukas, D., Pasricha, R., Lantsberg, I., & Schoenfeld, A. R. (2015). Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines. Cancer cell international, 1523. https://doi.org/10.1186/s12935-015-0175-3
Doonachar, Alana, et al. "Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines." Cancer cell international vol. 15 (2015): 23. doi: https://doi.org/10.1186/s12935-015-0175-3
Doonachar A, Gallo MD, Doukas D, Pasricha R, Lantsberg I, Schoenfeld AR. Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines. Cancer Cell Int. 2015 Feb 22;15:23. doi: 10.1186/s12935-015-0175-3. eCollection 2015. PMID: 25729330; PMCID: PMC4342814.
Copy Download .nbib Format: NLM
Share it on

Cancer Cell Int. 2015 Feb 22;15:23. doi: 10.1186/s12935-015-0175-3. eCollection 2015.

Differential effects of HIF-α isoforms on apoptosis in renal carcinoma cell lines.

Cancer cell international

Alana Doonachar, Michael D Gallo, Donald Doukas, Rajiv Pasricha, Igor Lantsberg, Alan R Schoenfeld

Affiliations

  1. Department of Biology, Adelphi University, One South Avenue, P.O. Box 701, Garden City, NY 11530-0701 USA.

PMID: 25729330 PMCID: PMC4342814 DOI: 10.1186/s12935-015-0175-3

Abstract

BACKGROUND: Germline mutations in the von Hippel-Lindau (VHL) tumor suppressor gene predispose individuals to clear cell renal carcinomas, hemangioblastomas, and pheochromocytomas. The VHL gene product forms an ubiquitin E3 ligase complex, with regulation of hypoxia-inducible factor alpha (HIF-α) as its best known function. Lack of VHL expression has been shown previously to sensitize renal cells to apoptosis caused by certain cellular stresses. In this report, the role of HIF-α in apoptosis was investigated using two parent VHL-null renal carcinoma cell lines.

METHODS: 786-O and RCC10 renal carcinoma cell lines with manipulated levels of VHL, HIF-1α, or HIF-2α were subjected to cellular stresses and analyzed by western blotting for the abundance of apoptotic markers.

RESULTS: Cell lines expressing mutant VHL proteins that were unable to regulate HIF-α had increased levels of apoptosis when irradiated with ultraviolet (UV) light. The influences of the two major isoforms of HIF-α, HIF-1α and HIF-2α, on apoptosis, were compared by creating cell lines in which levels of each isoform were modulated via short hairpin RNA interference. In UV-irradiated cells, HIF-2α expression was determined to promote apoptosis, whereas HIF-1α was anti-apoptotic. In cells deprived of either glucose or serum, HIF-1α expression was generally anti-apoptotic, while HIF-2α expression was observed to either promote apoptosis or have less of an influence on apoptosis, depending on the cell line used.

CONCLUSIONS: HIF-1α and HIF-2α exerted distinct effects in each of the conditions tested, with expression of HIF-1α largely blocking apoptosis and HIF-2α generally promoting apoptosis. These results reinforce that HIF-1α and HIF-2α have distinct biological roles and that their relative expression levels may influence some therapeutic interventions that are dependent on apoptosis.

Keywords: Apoptosis; Glucose starvation; HIF-alpha; Serum starvation; UV-irradiation; VHL

References

  1. Cell Death Differ. 1999 Nov;6(11):1067-74 - PubMed
  2. Mol Cell Biol. 1999 Feb;19(2):1289-300 - PubMed
  3. Nature. 1999 May 20;399(6733):271-5 - PubMed
  4. J Biol Chem. 2001 Nov 2;276(44):40599-605 - PubMed
  5. J Biol Chem. 2000 Aug 18;275(33):25733-41 - PubMed
  6. Cancer Res. 2005 Mar 15;65(6):2277-86 - PubMed
  7. Oncogene. 2000 Nov 16;19(48):5435-43 - PubMed
  8. Cancer Res. 2001 Sep 15;61(18):6669-73 - PubMed
  9. Cancer Cell. 2002 Apr;1(3):247-55 - PubMed
  10. Proc Natl Acad Sci U S A. 1998 Feb 3;95(3):993-8 - PubMed
  11. Cancer Cell. 2002 Sep;2(3):243-7 - PubMed
  12. J Virol. 1996 Aug;70(8):5701-5 - PubMed
  13. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8817-22 - PubMed
  14. Mol Cell Biol. 2003 Dec;23(24):9361-74 - PubMed
  15. Science. 1993 May 28;260(5112):1317-20 - PubMed
  16. PLoS Biol. 2003 Dec;1(3):E83 - PubMed
  17. Genes Dev. 1999 Jul 15;13(14 ):1822-33 - PubMed
  18. Cancer Cell. 2007 Apr;11(4):335-47 - PubMed
  19. Cancer Cell. 2008 Dec 9;14 (6):435-46 - PubMed
  20. Nat Cell Biol. 2000 Jul;2(7):423-7 - PubMed
  21. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12436-41 - PubMed
  22. Mol Cell Biol. 2005 Jul;25(13):5675-86 - PubMed
  23. Cancer Cell Int. 2007 Jun 28;7:13 - PubMed
  24. Toxicol Pathol. 2007 Jun;35(4):495-516 - PubMed
  25. Mol Cell Biol. 2014 Feb;34(4):739-51 - PubMed
  26. Oncogene. 2000 Nov 30;19(51):5851-7 - PubMed
  27. Nat Rev Cancer. 2011 Dec 15;12(1):9-22 - PubMed
  28. BMC Cancer. 2009 Jul 14;9:229 - PubMed
  29. Proc Natl Acad Sci U S A. 2012 Apr 10;109 (15):5669-74 - PubMed

Publication Types

Grant support