Extracellular signals in young and aging breast epithelial cells and possible connections to age-associated breast cancer development

Aging of human breast tissue is accompanied by certain structural and functional variations and several studies suggest a possible contribution of these changes to an aging-related breast cancer development. At the cellular level, aging of human mammary epithelial cells is associated with significant morphological and functional alterations such as an increased cell size and a reduced proliferation. Cellular senescence of HMEC cannot be explained by a single mechanism but represents an interaction of numerous extra- and intracellular events and the complexity of such orchestrating pathways is still hardly understood. Besides the contribution of reactive oxygen species and telomere dysfunction to aging, it is the aim of this mini-review, to compare distinct changes to extracellular signals by certain matrix metalloproteinases including MMP-7 and associated growth factor pathways mediated by HB- EGF activation in young and aging HMEC. Such changes can alter hormone receptor levels within aged HMEC, induce tissue fibrosis and promote epithelial-to-mesenchymal transition as a potential prerequisite for breast cancer development. Moreover, an accumulation of aging cells during the normal life span of the breast tissue may also substantially effect and interact with adjacent neighboring populations in the local microenvironment to provide optimized growth conditions which would also support neoplastic cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.