Oestrogen, acting via ERβ, limits ovarian granulosa cell proliferation and promotes their terminal differentiation into luteal cells. Few genes and proteins specifically activated by ERβ have been identified to date and thus we still do not have a complete understanding of its role in folliculogenesis and indeed in granulosa cell tumours (GCT).
Work undertaken by Simon during his PhD studies suggests that ERβ may be inhibitory to growth with signaling repressed in tumourigenesis via the NFkB signaling pathway. This is certainly the case in the COV434 and KGN granulosa cell tumour cell lines. These interactions appear to be ligand-specific and we are exploring a range of novel ERβ-specific ligands to further our studies.
We have a series of strategies in place aimed at understanding the role of this receptor both in vitro and in vivo using GCT-derived cells, primary GC cultures and transgenic mouse models. In addition, we have screened for interactions of the receptor with co-regulatory molecules and have a panel of novel interacting proteins that require full characterisation and represent data unique to our group.
Associate Professor Tom Jobling, Gynaecology Oncology, Monash Health
Professor John Katzenellenbogen, Professor Chemistry, University of Illinois, USA
Chu, S. Nishi, Y., Yanase, T., Nawata, H. and Fuller, P.J.Transrepression of estrogen receptor β signaling by nuclear factor-kB in ovarian granulosa cells. Molecular Endocrinology 18: 1919-1928, 2004.
Drummond, A.E. and Fuller, P.J.Activin and inhibin, estrogens and NFκB play roles in ovarian tumorigenesis. Is there crosstalk? Molecular and Cellular Endocrinology 359: 85-91, 2012.
Drummond, A.E. and Fuller, P.J.Ovarian actions of ERβ: an update. Seminars in Reproductive Medicine 30:32-38, 2012.
Chu, S., Jobling, T., Mamers, P., Burger, H.G. and Fuller, P.J.Estrogen receptor isoform gene expression in ovarian stromal and epithelial tumors. Journal of Clinical Endocrinology and Metabolism 85: 1200-1205, 2000.