PMID- 24092824
OWN - NLM
STAT- MEDLINE
DCOM- 20140414
LR  - 20181202
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Linking)
VI  - 98
IP  - 12
DP  - 2013 Dec
TI  - EGF-like growth factors induce COX-2-derived PGE2 production through ERK1/2 in 
      human granulosa cells.
PG  - 4932-41
LID - 10.1210/jc.2013-2662 [doi]
AB  - CONTEXT: Aberrant regulation of ovulation is one of the major causes of 
      infertility. In animal models, 3 epidermal growth factor (EGF)-like growth 
      factors, amphiregulin (AREG), betacellulin (BTC), and epiregulin (EREG), have 
      been shown to be involved in ovulation by regulating cyclooxygenase-2 (COX-2) 
      expression and prostaglandin E2 (PGE2) production. However, whether the same is 
      true in humans remains largely unknown. OBJECTIVE: Our objective was to 
      investigate the effects of AREG, BTC, and EREG on COX-2 expression and PGE2 
      production in human granulosa cells. DESIGN AND SETTING: SVOG cells are human 
      granulosa cells that were obtained from women undergoing in vitro fertilization 
      and immortalized with SV40 large T antigen. SVOG cells were used to investigate 
      the effect of AREG, BTC, and EREG on ovulation-related functions at an academic 
      research center. MAIN OUTCOME MEASURES: Levels of mRNA and protein were examined 
      by quantitative RT-PCR and Western blotting, respectively. The protein levels of 
      PGE2 were measured by ELISA. RESULTS: LH treatment upregulated AREG, BTC, EREG, 
      and COX-2. Knockdown of EGF receptor (EGFR) attenuated LH-induced COX-2 
      expression and PGE2 production. Treatment with AREG, BTC, and EREG upregulated 
      COX-2 expression and PGE2 production. The stimulatory effects of AREG, BTC, and 
      EREG on COX-2 expression and PGE2 production were blocked by inhibition of EGFR 
      activity and expression. AREG-, BTC-, and EREG-activated ERK1/2 signaling, but 
      not Akt signaling, was required for AREG-, BTC-, and EREG-induced COX-2 
      expression and PGE2 production. CONCLUSION: AREG, BTC, and EREG induced PGE2 
      production by upregulating COX-2 expression through ERK1/2 signaling in human 
      granulosa cells.
FAU - Fang, Lanlan
AU  - Fang L
AD  - PhD, FCAHS, FRSC, Department of Obstetrics and Gynaecology, Child and Family 
      Research Institute, University of British Columbia, Room 317, 950 West 28th 
      Avenue, Vancouver, British Columbia, Canada V5Z 4H4. peter.leung@ubc.ca.
FAU - Cheng, Jung-Chien
AU  - Cheng JC
FAU - Chang, Hsun-Ming
AU  - Chang HM
FAU - Sun, Ying-Pu
AU  - Sun YP
FAU - Leung, Peter C K
AU  - Leung PC
LA  - eng
GR  - Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131003
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (BTC protein, human)
RN  - 0 (Betacellulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Proteins)
RN  - 62229-50-9 (Epidermal Growth Factor)
RN  - 9002-67-9 (Luteinizing Hormone)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (PTGS2 protein, human)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - K7Q1JQR04M (Dinoprostone)
SB  - IM
MH  - Amphiregulin
MH  - Betacellulin
MH  - Cell Line, Transformed
MH  - Cyclooxygenase 2/chemistry/genetics/*metabolism
MH  - Dinoprostone/metabolism
MH  - EGF Family of Proteins
MH  - *Enzyme Induction
MH  - Epidermal Growth Factor/genetics/*metabolism
MH  - Epiregulin
MH  - ErbB Receptors/antagonists & inhibitors/genetics/metabolism
MH  - Female
MH  - Glycoproteins/genetics/*metabolism
MH  - Granulosa Cells/enzymology/*metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/genetics/*metabolism
MH  - Luteinizing Hormone/metabolism
MH  - *MAP Kinase Signaling System
MH  - RNA Interference
MH  - RNA, Messenger
MH  - RNA, Small Interfering
MH  - Recombinant Proteins/metabolism
MH  - Up-Regulation
EDAT- 2013/10/05 06:00
MHDA- 2014/04/15 06:00
CRDT- 2013/10/05 06:00
PHST- 2013/10/05 06:00 [entrez]
PHST- 2013/10/05 06:00 [pubmed]
PHST- 2014/04/15 06:00 [medline]
AID - jc.2013-2662 [pii]
AID - 10.1210/jc.2013-2662 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2013 Dec;98(12):4932-41. doi: 10.1210/jc.2013-2662. Epub 
      2013 Oct 3.