Scientific topics
Keywords
Gwendal Lazennec PhD, Director of Research
Course and current status
Present position: Group Leader (CNRS CR1) since december 1998. Main area of expertise: Chemokines, estrogen receptors and cancer
Laboratory: INSERM U844, Hôpital St Eloi, 80 rue Augustin Fliche, 34295, Montpellier, France
I. Post-doctoral Experience
* First post-doctoral position: (Jan 1996-Dec. 1997) in Pr. B.S. Katzenellenbogen's laboratory (University of Illinois, Urbana, USA). Work on the human estrogen receptor function.
* 2nd post-doctoral position: (Jan-Dec. 1998) in Pr. W. Wahli's laboratory (University of Lausanne, Switzerland). Work on peroxysome proliferator activated receptors (PPAR).
II. Education
- Baccalauréat D (Rennes, France) June 1987
- Master (University of Rennes, France) Sept 1992
- Ph.D.: University of Rennes, France Jan 4th, 1996.
- HDR (Hability to Direct Research) Nov 23rd, 2001
III. Awards
- 1996: Susan Komen Foundation
- 2007: Cancer Prize from the French Academy of Medecine
- 2008: Berthe Péan Prize from the French Academy of Medecine
Scientific summary
The goals of the team are double:
1. Decrypt the roles and mechanisms of action of estrogen receptor beta in breast, ovarian and prostate cancers
In industrial nations, cancers of the breast, the ovary and the prostate represent one of the first causes of mortality by cancer. It is thus essential to have a better understanding of the mechanisms of development of cancers to propose new therapies. Oestrogens are involved in the differentiation and the proliferation of the normal epithelial cells of the breast and the ovary, via their mediators, the receptors alpha and beta of the oestrogens (ERalpha and ERbeta). Until the discovery in 1996 of the beta receptor, ERalpha was considered as the unique isoforme and appeared as the mediator of the proliferative effects of the oestrogens. Several studies showed that the expression of ERbeta is weak in breast cancers with regard to normal tissues. The loss of expression of ERbeta during the carcinogenesis was also observed in the cancers of the ovary, the colon or the prostate.
Our team was the first one to show that the restoration of the expression of ERbeta in cells of breast cancer or prostate inhibits the proliferation and the invasive capacity of these cells, and comes along with an increase of the apoptosis. This suggests that ERbeta could play a role of tumor suppressor. Furthermore, we put in evidence a synergic anti-proliferative action between the inhibitors of histones déacétylases (HDACi) and ERbeta. We try now to determine what are the control mechanisms of the expression and the action of ERbeta at the molecular level and by the use of models of xenografts of luminescent cells to athymic mice.
2. Define the roles of mesenchymal stem cells and chemokines in breast and prostate cancers
The bone is an organ targets the main part of formation of metastases stemming from tumors of the breast or from the prostate. This process is incurable and entails pains and fractures. Mechanisms responsible for the variable aggressiveness of cancers remain for the moment poorly understood. The tumors of the breast express in approximately 70 % of the cases the receptor alpha of oestrogens (ERalpha). Interestingly, ER-negative breast cancers present a more pronounced aggressiveness than ER-positive breast cancers, notably in terms of formation of metastases. Particular attention is given to tumor microenvironment with the involvement of mesenchymal stem cells (MSC).
We showed that chemokines such IL-8 (CXCL8 ), MCP-1 (CCL2 ) and MIP-1beta (CCL4) were overexpressed in the ER-negative breast cancers. Furthermore, IL-8 is capable of increasing the capacity of invasion of the tumoral cells. The purpose of our work is to identify at the clinical level chemokines involved in the development of metastases, to validate these new targets by in vivo models of xenografted mice, transgenics and KO animals, to understand the mechanisms of control of the expression of these molecules and to propose new therapeutic strategies.
