- Publication date : 2017-04-06
Tremblay PG, Sirard MA. Transcriptomic analysis of gene cascades involved in protein kinase A and C signalling in the KGN line of human ovarian granulosa tumour cells1. Biol. Reprod. 2017;:. doi: 10.1093/biolre/iox024. PubMed PMID: 28383663.
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 signalling 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 tumour 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 signalling appeared to involve five major upstream regulators, namely EGF, TGFB1, VEGF, FGF2 and HGF. Genes associations with seven major ovarian functions were identified: PTGS2, IL8 and IL6 with inflammation; STAR, CYP11A1 and CYP19A1 with steroidogenesis; VEGFC, VEGFA and CXCR4 with angiogenesis; AREG, EGFR and SPRY2 with differentiation, BAX, BCL2L12 and CASP1 with apoptosis, CCND1, CCNB1 and CCNB2 with division and MMP1, MMP9 and TIMP1 with ovulation. These results indicate overall that signalling 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.