Original Article

Oncogene (2008) 27, 2365–2374; doi:10.1038/sj.onc.1210886; published online 29 October 2007

Immortalization of epithelial progenitor cells mediated by resveratrol

V P Pearce1,3, J Sherrell2, Z Lou3, L Kopelovich4, W E Wright3 and J W Shay3

  1. 1Department of Pharmacology and Neuroscience, UNT Health Science Center at Fort Worth, University of North Texas, Fort Worth, TX, USA
  2. 2School of Dentistry, University of Arizona, Phoenix, AZ, USA
  3. 3Department of Cell Biology, UT Southwestern Medical School, University of North Texas, Dallas, TX, USA
  4. 4Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, USA

Correspondence: Dr JW Shay, Department of Cell Biology, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd., Dallas, TX 75390-9039, USA. E-mail: Jerry.Shay@UTSouthwestern.edu

Received 13 September 2006; Revised 18 August 2007; Accepted 1 October 2007; Published online 29 October 2007.



Within the hierarchy of epithelial stem cells, normal progenitor cells may express regulated telomerase during renewal cycles of proliferation and differentiation. Discontinuous telomerase activity may promote increased renewal capacity of progenitor cells, while deregulated/continuous telomerase activity may promote immortalization when differentiation and/or senescent pathways are compromised. In the present work, we show that resveratrol activates, while progesterone inactivates, continuous telomerase activity within 24h in subpopulations of human Li–Fraumeni syndrome-derived breast epithelial cells. Resveratrol results in immortalization of mixed progenitor cells with mutant p53, but not human epithelial cells with wild type p53. Our results demonstrate the potential for renewing progenitor cells with mutant p53 to immortalize after continuous telomerase expression when exposed to certain environmental compounds. Understanding the effects of telomerase modulators on endogenous telomerase activity in progenitor cells is relevant to the role of immortalization in the initiation and progression of cancer subtypes.


telomerase, p53, progesterone, breast epithelial, aging