TY - JOUR
T1 - Regulation of proliferation and apoptosis by epidermal growth factor and protein kinase C in human ovarian surface epithelial cells
AU - McClellan, Maryanne
AU - Kievit, Paul
AU - Auersperg, Nelly
AU - Rodland, Karin
N1 - Funding Information:
1This work was supported by Grants CA-60738 and CA-78722 from the NIH National Cancer Institute (to K.D.R.) and in part by a grant from the Howard Hughes Medical Institute made to Reed College under the 1991 Undergraduate Biological Sciences Initiative (sabbatical support for M.M.). 2To whom reprint requests should be addressed. Fax: (503) 494-4253.
PY - 1999/2/1
Y1 - 1999/2/1
N2 - Epidermal growth factor (EGF) is produced in the ovary and influences proliferation of the malignant ovarian surface epithelium (OSE); yet its role in malignancy or in regulating the normal surface epithelium is unclear. In human OSE cells derived from primary cultures of normal tissue transfected with SV40 large T antigen (IOSE cells), EGF promoted survival but not proliferation. This survival effect was reversed by acute treatment with the phorbol ester, 12-0-tetradecanoyl-13-phorbol acetate (TPA) which alone markedly inhibited IOSE proliferation. We tested whether the activities of the mitogen-activated protein kinases (ERK1/2 and JNK1) varied in response to EGF, TPA, or combinations of these agonists and if the same treatments altered patterns of immediate early gene expression. Alone, EGF activated ERK1/2, increased and sustained levels of c-jun mRNA, but had almost no effect on JNK1 activation. Conversely, PKC activation resulted in a rapid, but transient induction of c-los RNA and of both kinases, JNK1 and ERK2. When combined, EGF and TPA further enhanced the phosphorylation of both enzymes despite inhibiting survival. Though JNKs and ERKs are thought to transduce opposing cellular responses, in IOSE cells, robust costimulation of the JNK and ERK pathways may redirect the survival message.
AB - Epidermal growth factor (EGF) is produced in the ovary and influences proliferation of the malignant ovarian surface epithelium (OSE); yet its role in malignancy or in regulating the normal surface epithelium is unclear. In human OSE cells derived from primary cultures of normal tissue transfected with SV40 large T antigen (IOSE cells), EGF promoted survival but not proliferation. This survival effect was reversed by acute treatment with the phorbol ester, 12-0-tetradecanoyl-13-phorbol acetate (TPA) which alone markedly inhibited IOSE proliferation. We tested whether the activities of the mitogen-activated protein kinases (ERK1/2 and JNK1) varied in response to EGF, TPA, or combinations of these agonists and if the same treatments altered patterns of immediate early gene expression. Alone, EGF activated ERK1/2, increased and sustained levels of c-jun mRNA, but had almost no effect on JNK1 activation. Conversely, PKC activation resulted in a rapid, but transient induction of c-los RNA and of both kinases, JNK1 and ERK2. When combined, EGF and TPA further enhanced the phosphorylation of both enzymes despite inhibiting survival. Though JNKs and ERKs are thought to transduce opposing cellular responses, in IOSE cells, robust costimulation of the JNK and ERK pathways may redirect the survival message.
UR - http://www.scopus.com/inward/record.url?scp=0033080444&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0033080444&partnerID=8YFLogxK
U2 - 10.1006/excr.1998.4328
DO - 10.1006/excr.1998.4328
M3 - Article
C2 - 9925763
AN - SCOPUS:0033080444
SN - 0014-4827
VL - 246
SP - 471
EP - 479
JO - Experimental Cell Research
JF - Experimental Cell Research
IS - 2
ER -