Pregnancy, lactation and mammary gland involution. Their involvement in tumor development

EDITH KORDON

Guelph, Toronto, Canada

Simposio; Inaugural Summer Cancer Research Symposium; 2008

University of Guelph, Ontario Veterinary College

 It is well known that early first childbirth reduces the risk of developing breast cancer. However, epidemiological studies show that in pre-menopausal women there is a transient risk for developing breast cancer in the first 5 years following pregnancy. Tumors that appear in such a period are called pregnancy-associated breast cancers (PABC).  There are not many animal models that are useful for studying the initiation and progression of mammary tumors in the context of pregnancy, lactation and involution of the mammary gland. The pregnancy-dependent mammary tumors induced by the retrovirus MMTV (mouse mammary tumor virus) offer that possibility. During the last 10 years, our group has studied the biology of these tumors, which are estrogen-dependent in their early stages to later progress to a hormone-independent behavior. We have demonstrated that this progression occurs associated to the loss of estrogen and progesterone receptor expression and to the selection of early occurring virus insertions. By inverse-PCR we were able to cloned-out some of these MMTV insertion sites. Our most recent results are focused in the analysis of the biological activity and expression regulation of two genes found in those loci: R-sponding 1 and b1-integrin. In addition, it has been indicated that it is not pregnancy or parturition, but mammary involution what increases the risk of PABC. Therefore, we are analyzing different factors that play a role in the transition from lactation to involution and could also be relevant for breast cancer development. Our studies are mainly focused in inflammatory cytokines as LIF and TNFa, transcription factors as Stat3 and Stat5, and mRNA stability regulators as TTP. In addition, we are investigating the role that mechanical stress can exert on mammary epithelial cells to trigger events that can lead to either apoptosis or transformation of mammary epithelial cells.