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  • Phone : +33157278404
  • Location : Paris, France
Last update 2015-08-18 17:37:15.428

Céline Guigon PhD Cell Signaling, Endocrinology & Reproductive Biology

Course and current status

Current position:

Research Associate; CR1 Inserm, University Paris 7, CNRS-EAC4413, Paris, France.

 

Education:

2000-2004    PhD Cell Signaling, Endocrinology & Reproductive Biology, University Paris11, Le Kremlin-Bicêtre, France.

1999-2000    Master in Physiology of Reproduction, University Paris 6, Paris, France.

1998-1999   Bachelor in Cellular Biology and Physiology, University Paris 6, Paris, France.

 

Chronology of Employment:

Jan-Sept 2005:  Postdoctoral Fellow, Laboratory of Physiology and Physiopathology, University Paris 6, Paris, France.

2005-2010: Postdoctoral Fellow, Gene Regulation Section, Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health

Nov 2010-Oct 2011: Postdoctoral Fellow, Physiology of Gonadotropic Axis Group, Unit of Functional and Adaptive Biology, University Paris Diderot-Paris, France.

 

Honors and Other Special Scientific Recognition: 

2010-Fondation pour la Recherche Medicale (FRM) postdoctoral fellowship

2008-Exceptional Stipend Increase

2008-NIH FARE 2009 award 

2007-Annual Meeting of the Endocrine Society Travel Award. 

2003-Cancer Association Research (ARC) Doctoral Fellowship.

2002-Annual Meeting of the French Society of Endocrinology (SFE) Travel Fellowship.

2002-American Society for the Study of Reproduction (SSR) Travel Fellowship.

2000-French Ministery of Research Doctoral Fellowship.

Scientific summary

Research in my group mainly focuses on estrogen signaling in the mammalian ovary with a special emphasis on non-classical actions of estrogens in granulosa cell tumours (GCT). This malignancy affects women of all ages, with two distinct clinical presentations, the adult and juvenile forms. Most juvenile cases are diagnosed early and their prognosis is generally good, though recurrences and metastases have been reported. However, in the adult cases of GCT, 80% of patients with advanced disease die of the consequences of their tumour. The particularity of this disease is its high rate of recurrence, even when the diagnosis is established at an early stage. Besides, these tumours have a tendency to late recurrence, with latency after primary tumour treatment of up to 37 years. Chemotherapy has limited success, and surgery remains the main therapeutic approach. 

17β-estradiol (E2) is found elevated in ~70% of patients. However, whether E2 could play a role in GCT development and progression was not known. This question is particulary relevant given that estrogens play a key role in regulating ovarian function, and alteration in its signaling pathways may contribute to ovarian cancer. We therefore investigated the possibility that E2 could regulate ovarian function and tumorigenesis. 

Our cell-based studies with human cell lines revealed that this steroid does not alter human GCT cell growth and that it inhibits metastatic GCT cell migration and invasion in vitro. This is in marked contrast with what is usually found in other gynaecological diseases where a tumor-promoting role of estrogens has been documented. Besides, we discovered that estrogens signal via non-genomic actions in GCT cells to rapidly and selectively repress ERK1/2 activity in metastatic GCT cells. This pathway, which is overactivated in GCT, plays a major role in cell migration and invasion. These data therefore suggest that estrogens would specifically repress ERK1/2 pathway via non-genomic signaling to inhibit GCT metastasis spreading. By studying the possible ER involved in estrogen-induced ERK1/2 repression, we found that it involves none of the classical ERs, but a member of the seven-transmembrane G-protein coupled receptor (GPCR) family, GPR30 also named GPER1 (for G-protein coupled estrogen receptor). Analyses of human GCT samples by tissue-microarrays in collaboration with the GINECO network revealed that a majority of these tumors expresses GPER1. These data are of particular interest as they suggest that estrogens would have a protective role on this form of ovarian cancer by acting through novel non-genomic modes of action never reported to date. Additional studies are ongoing on preclinical animal models to confirm in vivo the potential benefit of using estrogen therapy to prevent GCT progression.

This work has been supported by grants from the Research Executive Agency of the European Commission (Marie Curie Reintegration grant, ESTROVARYTUMOUR # 276970), by La Ligue Contre Le Cancer and by La Fondation Pour la Recherche Médicale (FRM, programme espoir de la recherche). 

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