Projects
18: Endocrine disruptors and breast carcinogenesis: A new mouse model to assess estrogen receptor-dependent and -independent effects in vivo.
Endocrine disruptors and breast carcinogenesis.
Hormones control breast development and contribute to breast carcinogenesis. This project intends to analyze with an in vivo model how exposure to endocrine disruptors during puberty affects mammary gland development. In addition, the role of estrogen receptors in the process will be assessed.
Brisken Cathrin, Swiss Institute for Experimental Cancer Research (ISREC), Epalinges/Lausanne
e-mail: cathrin.brisken@isrec.unil.ch
Background
Breast cancer strikes one out of eight women in Switzerland. An important but as yet little-understood interconnection exists between the reproductive hormones and molecular determinants of breast development, and breast cancer risk. Furthermore, the contribution of endocrine disruptors to the breast cancer problem and the mechanisms underlying their mammotropic functions remain unclear.
Aim
This project intends to analyze the effects of endocrine disruptors on mammary gland development in the mouse and to assess the extent to which they depend on intact estrogen receptor signalling. Large-scale measurements of gene expression in the breast will be used to uncover subtle effects exerted by these substances and to determine whether they deregulate pathways involved in the control of breast development and/or carcinogenesis.
Significance
In contrast to existing in vitro assays for estrogenic activity, our in vivo model adequately reflects the high complexity of direct and indirect effects elicited by endocrine disruptors in the living organism. It allows us to test the hypothesis that xenoestrogens may affect development of the mammary gland, which eventually results in carcinogenesis by deregulating local developmental signalling pathways. The project will help to identify molecular markers of endocrine disruptor action which can subsequently be used to characterize new substances with regard to their mammotropic potential.