PMID- 28383663
OWN - NLM
STAT- MEDLINE
DCOM- 20180312
LR  - 20180312
IS  - 1529-7268 (Electronic)
IS  - 0006-3363 (Linking)
VI  - 96
IP  - 4
DP  - 2017 Apr 1
TI  - Transcriptomic analysis of gene cascades involved in protein kinase A and C 
      signaling in the KGN line of human ovarian granulosa tumor cellsdagger.
PG  - 855-865
LID - 10.1093/biolre/iox024 [doi]
AB  - The developmental competence of an oocyte is its capacity to resume maturation, 
      undergo successful fertilization, and reach the blastocyst stage. This competence 
      is acquired through interaction with somatic cells of the follicle. Cumulus and 
      granulosa cells support oocyte development, while the oocyte influences 
      follicular cell growth and differentiation. Studies suggest that 
      follicle-stimulating hormone and luteinizing hormone play an essential role in 
      oocyte competence acquisition through signaling initiated by protein kinases A 
      and C (PKA and PKC) in granulosa cells. Using a microarray and RT-qPCR, the 
      transcriptome of human granulosa-like tumor cells (KGN) treated for 24 h with 
      forskolin (FSK) or phorbol 12-myristate 13-acetate (PMA) was analyzed to 
      determine the effects of PKA and PKC stimulation on gene expression. 
      Protein-kinase-driven signaling appeared to involve five major upstream 
      regulators, namely epidermal growth factor (EGF), transforming growth factor beta 
      1 (TGFbeta1), vascular endothelial growth factor (VEGF), basic fibroblast growth 
      factor (FGF2), and hepatocyte growth factor (HGF). Gene associations with seven 
      major ovarian functions were identified: Prostaglandin- endoperoxide synthase 2 
      (PTGS2), interleukin 8 (IL8), and interleukin 6 (IL6) with inflammation; 
      Steroidogenic acute regulatory protein (STAR), cytochrome P450scc (CYP11A1), and 
      cytochrome P450 family 19 subfamily A member 1 (CYP19A1) with steroidogenesis; 
      Vascular endothelial growth factor C (VEGFC), Vascular endothelial growth factor 
      A (VEGFA), and C-X-C chemokine receptor type 4 (CXCR4) with angiogenesis; 
      Amphiregulin (AREG), epidermal growth factor receptor (EGFR), and sprouty RTK 
      signaling antagonist 2 (SPRY2) with differentiation, BCL2 associated X (BAX), 
      BCL2 like 12 (BCL2L12), and caspase 1(CASP1) with apoptosis, Cyclin D1 (CCND1), 
      cyclin B1 (CCNB1), and cyclin B2 (CCNB2) with division; and Matrix 
      metalloproteinase-1 (MMP1), Matrix metallopeptidase 9 (MMP9), and TIMP 
      metallopeptidase inhibitor 1 (TIMP1) with ovulation. Overall, these results 
      indicate that signaling via both PKA and PKC potentiates gene regulation of 
      functions such as inflammation and apoptosis, while functions such as 
      differentiation, ovulation and angiogenesis are partial to one kinase or the 
      other. These results improve understanding of the pathways underlying the most 
      important changes that occur in the follicle prior to ovulation.
CI  - (c) The Authors 2017. Published by Oxford University Press on behalf of Society for 
      the Study of Reproduction. All rights reserved. For permissions, please 
      journals.permissions@oup.com.
FAU - Tremblay, Patricia G
AU  - Tremblay PG
FAU - Sirard, Marc-Andre
AU  - Sirard MA
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (RNA, Messenger)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 2.7.11.13 (Protein Kinase C)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism
MH  - Estradiol/biosynthesis
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Granulosa Cell Tumor/*metabolism
MH  - Humans
MH  - Protein Array Analysis
MH  - Protein Kinase C/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Reproducibility of Results
MH  - Signal Transduction
MH  - *Transcriptome
OTO - NOTNLM
OT  - granulosa cells
OT  - ovary
OT  - signaling
EDAT- 2017/04/07 06:00
MHDA- 2018/03/13 06:00
CRDT- 2017/04/07 06:00
PHST- 2017/03/02 00:00 [received]
PHST- 2017/04/03 00:00 [accepted]
PHST- 2017/04/07 06:00 [pubmed]
PHST- 2018/03/13 06:00 [medline]
PHST- 2017/04/07 06:00 [entrez]
AID - 3102958 [pii]
AID - 10.1093/biolre/iox024 [doi]
PST - ppublish
SO  - Biol Reprod. 2017 Apr 1;96(4):855-865. doi: 10.1093/biolre/iox024.