Role of post-lactational involution in the protective effect against breast cancer induced by early pregnancy.
Ponente: Adrián Blanco Gómez
Centro de Investigación del Cáncer (CIC-IBMCC), laboratorio 7
Fecha: 22/06/2017 - 22/06/2017
Salón de Actos del Centro de Investigación del Cáncer
Reproductive history is one of the most important epidemiological factors associated with breast cancer. Pregnancy at early age exerts a clear protective effect against breast cancer, and this phenomenon is conserved among mammalian species, such as the mouse. Pregnancy-induced risk reduction is enhanced by the number of pregnancies and by breastfeeding for an extended period of time. In the case of hereditary breast cancer associated with a mutation in BRCA1, the protective effect of pregnancy has been a matter of controversy, but several independent studies have reported this association in humans.
Taking all this into account, our main goal is to identify the molecular and cellular mechanisms responsible for the protection that pregnancy exerts against breast cancer using the Brca1-mutated breast cancer mouse model generated by Jonkers et al. (Brca1f/f, Trp53f/f, K14Cre). We are especially interested in the process of post-lactational involution and its importance for the protective effect of early pregnancy against breast cancer, as the modulation of this process may modify the resultant risk of the disease. We have found that the protective effect of early pregnancy is conserved in this model of Brca1-mutated breast cancer, and parous mice had lower incidence of mammary tumours after a longer time of latency than their nulliparous counterparts. Furthermore, breastfeeding increased the protective effect induced by parity alone, as parous mice that breastfed their pups had lower tumor multiplicity. As a result of pregnancy and post-lactational involution, mammary glands from parous mice showed a decrease in the accumulation rate of cells with recombined Trp53 and Brca1, as well as changes in epithelial cells subpopulations. Finally, we have found that pharmacological enhancement of post-alctational involution is a feasible strategy to increase the protective effect induced by pregnancy in these mice.