Transcription, environment and cancer (TREC)

The impact of environment contaminants on human health is a growing concern. Many natural and synthetic chemicals present in the environment and in food are suspected to interfere with steroid hormones and could exert adverse effects on the organism, leading to endocrine disruption. These compounds are generally termed endocrine-disrupting chemicals (EDCs) and are from different sources such as pesticides, plasticizers, pharmaceutical and cosmetic industries, heavy metals, incineration… Numbers of studies have reported a variety of reproductive alterations and appearance of adverse health effects in human, aquatic and wildlife species living within or near contaminated areas.

Our aim is to develop the understanding of EDC actions at transcriptional and epigenetic levels by using different cell-based models. Moreover, since the amount of persistent chemicals has increased over the last 20 years, we have investigated for a long time in the development of high-throughput screening methods.

Among EDCs, particularly, xeno-estrogens have been suspected as a potential risk factor for breast cancer. Indeed, as for natural estrogens, a prolonged exposure to xeno-estrogens may be prejudicial, in increasing the risk of breast cancer. Although each xeno-estrogen is absorbed in very small amounts, these substances are of concern because (i) they are persistent and widespread (in the environment and diet), (ii) they could act additively or synergistically as mixtures and  (iii) their concentrations can be elevated in the organism, where they are able to accumulate in certain tissues.Our project specifically targets the nuclear estrogen receptors (ERs) and their target genes that are mainly implied in growth and migration of breast cancer cells. The comprehension of the molecular mechanisms of the action of some of EDCs (found in environment or in food) would thus make it possible to establish a link between EDCs and the increase in breast cancer number. The secretion of some cytokines as well as the state of DNA methylation/demethylation, histone acetylation/methylation of certain gene promoters would therefore constitute a new biomarker of the exposure of the populations to chemical contaminations, making it possible to forecast the sensitivity to the development of breast cancer.

Moreover, in collaboration with a local industrial research group, we are investigating the potential estrogenic / antiestrogenic effects of new  compound classes in order to identify new bioactive ingredients for developing nutritional supplements or nutraceutical products used in the health food market or in chronic diseases.

Modes of action of xeno-estrogens