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Immortalization of epithelial progenitor cells mediated by resveratrol.

ABSTRACT: 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 24 h 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.

SUBMITTER: Pearce VP

PROVIDER: S-EPMC3397201 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Immortalization of epithelial progenitor cells mediated by resveratrol.

Pearce V P VP Sherrell J J Lou Z Z Kopelovich L L Wright W E WE Shay J W JW

Oncogene 20071029 17

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 t ...[more]

PMID: 17968319

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Project description:Nasopharyngeal carcinoma (NPC) is common among southern Chinese including the ethnic Cantonese population living in Hong Kong. Epstein-Barr virus (EBV) infection is detected in all undifferentiated type of NPC in this endemic region. Establishment of stable and latent EBV infection in premalignant nasopharyngeal epithelial cells is an early event in NPC development and may contribute to its pathogenesis. Immortalized primary nasopharyngeal epithelial cells represent an important tool for investigation of EBV infection and its tumorigenic potential in this special type of epithelial cells. However, the limited availability and small sizes of nasopharyngeal biopsies have seriously restricted the establishment of primary nasopharyngeal epithelial cells for immortalization. A reliable and effective method to immortalize primary nasopharyngeal epithelial cells will provide unrestricted materials for EBV infection studies. An earlier study has reported that Bmi-1 expression could immortalize primary nasopharyngeal epithelial cells. However, its efficiency and actions in immortalization have not been fully characterized. Our studies showed that Bmi-1 expression alone has limited ability to immortalize primary nasopharyngeal epithelial cells and additional events are often required for its immortalization action. We have identified some of the key events associated with the immortalization of primary nasopharyngeal epithelial cells. Efficient immortalization of nasopharyngeal epithelial cells could be reproducibly and efficiently achieved by the combined actions of Bmi-1 expression, activation of telomerase and silencing of p16 gene. Activation of MAPK signaling and gene expression downstream of Bmi-1 were detected in the immortalized nasopharyngeal epithelial cells and may play a role in immortalization. Furthermore, these newly immortalized nasopharyngeal epithelial cells are susceptible to EBV infection and supported a type II latent EBV infection program characteristic of EBV-infected nasopharyngeal carcinoma. The establishment of an efficient method to immortalize primary nasopharyngeal epithelial cells will facilitate the investigation into the role of EBV infection in pathogenesis of nasopharyngeal carcinoma.

Dataset Information

Immortalization of epithelial progenitor cells mediated by resveratrol.

Publications

Immortalization of epithelial progenitor cells mediated by resveratrol.

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