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United States Department of Agriculture

Agricultural Research Service

Research Project: IDENTIFICATION OF HOST IMMUNE FACTORS AND INTERVENTION STRATEGIES FOR MASTITIS Title: Cellular calcium dynamics in lactation and breast cancer: From physiology to pathology

Authors
item Cross, Brandie -
item Breitwieser, Gerda -
item Reinhardt, Timothy
item Rao, Rajini -

Submitted to: American Journal of Physiology - Cell Physiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: November 11, 2013
Publication Date: March 15, 2014
Citation: Cross, B.M., Breitwieser, G.E., Reinhardt, T.A., Rao, R. 2014. Cellular calcium dynamics in lactation and breast cancer: From physiology to pathology. American Journal of Physiology - Cell Physiology. 306(6):C515-C526.

Interpretive Summary: Lactation in is critical to developing humans and other mammals, as milk is the sole source of nutrition for the neonate. One of the major and key nutrients in milk is calcium (required for bone growth) but the mechanism by which calcium arrives in milk in large quantities has been unknown. Furthermore it is known that in breast cancer micro-calcifications (micro-calcium deposits) are defining characteristics of breast cancer in humans. This invited review summarizes what is current state of the art knowledge about how calcium is transported into milk along with detailing the normal molecular pathways key to milk calcium transport. The second part of the scientific review discusses how dysregulation of normal breast calcium transport pathways may contribute to breast cancer development and the pathological characteristics of breast cancer seen in mammograms such as micro-calcifications. The review summarizes what is know about breast calcium transport in a way that provides usable information for understanding calcium’s role in human breast cancer as well as possibly the underlying mechanisms important to calcium transport diseases in dairy cattle.

Technical Abstract: Breast cancer is the second leading cause of cancer mortality in women, estimated at nearly 40,000 deaths and more than 230,000 new cases diagnosed in the U.S. this year alone. One of the defining characteristics of breast cancer is the radiographic presence of microcalcifications. These palpable mineral precipitates are commonly found in the breast after formation of a tumor. Since free Ca2+ plays a crucial role as a second messenger inside cells, we hypothesize that these chelated precipitates may be a result of dysregulated Ca2+ secretion associated with tumorigenesis. Transient and sustained elevations of intracellular Ca2+ regulate cell proliferation, apoptosis and cell migration, and offer numerous therapeutic possibilities in controlling tumor growth and metastasis. During lactation, a developmentally determined program of gene expression controls the massive transcellular mobilization of Ca2+ from the blood into milk by the coordinated action of Calcium Transporters, including pumps, channels, sensors and buffers, in a functional module that we term CALTRANS. Here we assess the evidence implicating genes that regulate free and buffered Ca2+ in normal breast epithelium and cancer cells, and discuss mechanisms that are likely to contribute to the pathological characteristics of breast cancer.

Last Modified: 8/27/2014
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