TY - JOUR
T1 - IEX-1, an immediate early gene, increases the rate of apoptosis in keratinocytes
AU - Schilling, D.
AU - Pittelkow, M. R.
AU - Kumar, R.
N1 - Funding Information:
We thank Karen Squillace for excellent technical assistance. Supported by NIH grants, DK 25409, DK 58546 and AR-27032 (to R Kumar) and the Mayo Foundation (R Kumar and MR Pittelkow).
PY - 2001/11/29
Y1 - 2001/11/29
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Cell stress
KW - Cellular growth
KW - IEX-1
KW - Immediate early gene
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U2 - 10.1038/sj.onc.1204965
DO - 10.1038/sj.onc.1204965
M3 - Article
C2 - 11753682
AN - SCOPUS:0035969648
SN - 0950-9232
VL - 20
SP - 7992
EP - 7997
JO - Oncogene
JF - Oncogene
IS - 55
ER -