Downregulation of 14-3-3σ prevents clonal evolution and leads to immortalization of primary human keratinocytes

Elena Dellambra, Osvaldo Golisano, Sergio Bondanza, Emanuela Siviero, Pedro Lacal, Marta Molinari, Stefania D'Atri, Michele De Luca

Research output: Contribution to journalArticlepeer-review

Abstract

In human epidermal keratinocytes, replicative senescence, is determined by a progressive decline of clonogenic and dividing cells. Its timing is controlled by clonal evolution, that is, by the continuous transition from stem cells to transient amplifying cells. We now report that downregulation of 14-3-3σ, which is specifically expressed in human stratified epithelia, prevents keratinocyte clonal evolution, thereby forcing keratinocytes into the stem cell compartment. This allows primary human keratinocytes to readily escape replicative senescence. 14-3-3σ-dependent bypass of senescence is accompanied by maintenance of telomerase activity and by downregulation of the p16(INK4a) tumor suppressor gene, hallmarks of keratinocyte immortalization. Taken together, these data therefore suggest that inhibition of a single endogenous gene product fosters immortalization of primary human epithelial cells without the need of exogenous oncogenes and/or oncoviruses.

Original languageEnglish
Pages (from-to)1117-1129
Number of pages13
JournalJournal of Cell Biology
Volume149
Issue number5
DOIs
Publication statusPublished - May 29 2000

Keywords

  • Immortalization
  • p16(INK4a)
  • Senescence
  • Sterm cells
  • Telomerase
  • Transformation

ASJC Scopus subject areas

  • Cell Biology

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