The main objective of our team is to decipher the molecular mechanisms of hormone signaling by nuclear receptors (NRs). These NRs are involved in the proliferation of hormone-dependant cancer (breast and prostate) which constitute major challenges of public health. Following our recent data, our projects are focused on two types of regulators of NR activity : environmental ligands and transcription cofactors.

The first goal is to identify endocrine disruptors which interfere with hormone signaling. Such molecules present in various environmental or biological samples (river water and sediments, adipose tissues from patients with breast cancer) will be characterized using bioluminescent cell lines established in our laboratory. The various active molecules will be identified and further characterized in vivo on the bioluminescent cells grafted on nude mice.

The second goal deals with the control of NR activity and more precisely with the study of the transcription coregulator RIP140 (Receptor interacting protein of 140 kDa). We plan to analyze : 1) the mechanism of action of RIP140 at the transcriptional level (regulation of NR and other transcription factors activity, characterization of RIP140 partners) 2) the regulation of RIP140 gene expression (at the transcriptional and post-transcriptional levels) and activity (role of post-translational modifications)
3) the alterations of RIP140 gene in different biological samples (loss of heterozygosity and single nucleotide polymorphisms) 4) the role of RIP140 in cancer cells (regulation of cell cycle and proliferation, identification of target genes…) and transgenic mice (impact on mammary gland and prostate carcinogenesis).

The project main goal is to improve knowledge on nuclear receptor action at the level of gene expression and tumor growth. It combines both cognitive and applied aspects and should provide new data with implications in cancer biology and treatment:

characterization of new endocrine disruptors which activate nuclear receptors and participate in carcinogenesis (strong implications in term of therapy and cancer prevention)
deciphering of the molecular mechanisms involved in transcriptional hormonal signaling (better understanding of the mitogenic effects of hormones and of the molecular mechanisms of antihormone resistance)
identification of new markers for prognosis or diagnosis which could be used in the treatment of hormone-dependent cancers and the development of new combination of therapeutic agents which could improve the inhibition of cancer cell proliferation.