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Oncol Lett. 2012 Jan;3(1):224-228. doi: 10.3892/ol.2011.458. Epub 2011 Oct 21.

Effects of activation of AMPK on human breast cancer cell lines with different genetic backgrounds.

Oncology letters

Omar S El-Masry, Barry L Brown, Pauline R M Dobson

Affiliations

  1. Department of Molecular Biology and Biotechnology, University of Sheffield, Western Bank, Sheffield S10 2TN, UK.

PMID: 22740885 PMCID: PMC3362498 DOI: 10.3892/ol.2011.458

Abstract

Breast cancer remains a therapeutic challenge, and this has intensified the search for new drug targets. The AMP-activated protein kinase (AMPK) signalling pathway is emerging as having potential for intervention. We assessed the possible different effects of AMPK action on breast cancer cells by studying their impact on proliferation, apoptosis and the mitochondrial membrane potential in three breast cancer cell lines (MCF-7, MDA-MB-231 and T47D) differing in their p53 and estrogen receptor (ER) status. Activation of AMPK by 5-aminoimidazole carboxamide ribonucleotide (AICAR) and phenformin elicited clear anti-proliferative effects in all breast cancer cell lines, but with differences in sensitivity. However, the anti-proliferative effects were accompanied by varying responses between the different cells, with a marked cell cycle arrest effect in T47D cells and an apoptotic effect in MCF-7 and MDA-MB-231 cells. The mitochondrial apoptotic pathway was potentially involved in all cell lines. These results suggest that AMPK potentially serves as a therapeutic target in breast cancer, but one which may be dependent on the genetic background of the cancer cells.

References

  1. Biochem Biophys Res Commun. 2004 Aug 13;321(1):161-7 - PubMed
  2. Breast Cancer Res. 2007;9(5):213 - PubMed
  3. Eur J Endocrinol. 2009 Nov;161(5):655-62 - PubMed
  4. Biochim Biophys Acta. 2007 Jan;1775(1):63-75 - PubMed
  5. Front Biosci (Landmark Ed). 2009 Jan 01;14:19-44 - PubMed
  6. Life Sci. 2003 Dec 19;74(5):643-50 - PubMed
  7. Endocr Relat Cancer. 2006 Jun;13(2):279-92 - PubMed
  8. Trends Pharmacol Sci. 2005 Feb;26(2):69-76 - PubMed
  9. Cancer Res. 1998 Jun 1;58(11):2353-8 - PubMed
  10. Cancer Res. 2003 Oct 15;63(20):6815-24 - PubMed
  11. J Clin Invest. 2001 Oct;108(8):1167-74 - PubMed
  12. EMBO J. 2004 Feb 25;23(4):833-43 - PubMed
  13. J Biol Chem. 2005 Nov 25;280(47):39582-93 - PubMed
  14. Toxicol Pathol. 2007 Jun;35(4):495-516 - PubMed
  15. Mol Cancer. 2007 Jul 10;6:46 - PubMed
  16. Nat Rev Cancer. 2004 Oct;4(10):793-805 - PubMed
  17. Mol Cancer. 2008 May 12;7:37 - PubMed

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