IEX-1, an immediate early gene, increases the rate of apoptosis in keratinocytes

D. Schilling, M. R. Pittelkow, R. Kumar

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

IEX-1, an immediate early gene, is widely expressed in epithelial and endothelial tissues, and is altered by a variety of growth regulatory factors. We have shown that expression of IEX-1 in keratinocytes increases the growth rate of these cells. The effects of IEX-1 on apoptosis, however, are unclear. To clarify the effects of IEX-1 on apoptosis, we investigated the effects of IEX-1 expression in keratinocytes (HaCaT cells) in the basal state and after the induction of cellular stress. Under normal, non-stressed conditions, both control (HaCaT) and IEX-1-transfected (IEX-HaCaT) cell lines showed no significant differences in the activity of a key apoptotic enzyme, caspase 3 despite significantly higher levels of IEX-1 expression. IEX-HaCaT cells grew faster than HaCaT cells. When both cell lines were irradiated with ultraviolet B radiation, caspase 3 activity increased to a greater extent in the IEX-HaCaT cells than in HaCaT cells. Camptothecin increased caspase 3 activity twice as much in the IEX-HaCaT cells when compared to HaCaT cells. When histone-complex DNA fragments were measured in IEX-HaCaT or HaCaT cells following UVB irradiation or treatment with camptothecin, significantly higher amounts of nucleosomes were seen in the IEX-HaCaT transfected cells. Likewise, serum deprivation induced higher degrees of apoptosis in IEX-HaCaT cells than in HaCaT cells. We conclude that overexpression of IEX-1 in HaCaT keratinocytes increases the growth rate of cells under basal conditions; in the basal state the rate of apoptosis is unchanged. However, the rate of apoptosis increases in IEX-1 overexpressing HaCaT keratinocytes after cells are subjected to stress.

Original languageEnglish (US)
Pages (from-to)7992-7997
Number of pages6
JournalOncogene
Volume20
Issue number55
DOIs
StatePublished - Nov 29 2001

Keywords

  • Apoptosis
  • Cell stress
  • Cellular growth
  • IEX-1
  • Immediate early gene

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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