Interactions between luminal epithelial cells and their surrounding microenvironment govern the normal development and function of the mammary gland. Alter- ations of these interactions can induce abnormal intracel- lular signaling pathways that affect the development and progression of breast tumors. One critical component of mammary gland development, as well as breast cancer progression, is the expression of estrogen receptors. In a previous study using cultured nonmalignant mammary epithelial cells, we found that the basement membrane molecules, laminin-1 and collagen-IV, were involved in maintenance of estrogen receptor (ER) expression, and that this response could be interfered with by disrupting cell-extracellular matrix adhesion. Here we use phenotyp- ically normal mammary epithelial SCp2 cells to dissect the promoter region of the ER-alpha that is involved in the selective response to basement membrane. We also analyze the alteration of this response in SCg6 cells, a malig- nant cell line that shares a common lineage with the SCp2 cells, to provide insight into the relative overexpression of ER-alpha and the unresponsiveness to basement membrane regulation found in those malignant cells. Evidence is presented to show the relevance of the cross-talk between different signaling pathways in the constitution of a functional tissue organization and how this integration may be disrupted in the malignant phenotype.

Malignant mammary cells acquire independence from extracellular context for regulation of estrogen receptor alpha.

Weisz, Alessandro
Conceptualization
;
2004-01-01

Abstract

Interactions between luminal epithelial cells and their surrounding microenvironment govern the normal development and function of the mammary gland. Alter- ations of these interactions can induce abnormal intracel- lular signaling pathways that affect the development and progression of breast tumors. One critical component of mammary gland development, as well as breast cancer progression, is the expression of estrogen receptors. In a previous study using cultured nonmalignant mammary epithelial cells, we found that the basement membrane molecules, laminin-1 and collagen-IV, were involved in maintenance of estrogen receptor (ER) expression, and that this response could be interfered with by disrupting cell-extracellular matrix adhesion. Here we use phenotyp- ically normal mammary epithelial SCp2 cells to dissect the promoter region of the ER-alpha that is involved in the selective response to basement membrane. We also analyze the alteration of this response in SCg6 cells, a malig- nant cell line that shares a common lineage with the SCp2 cells, to provide insight into the relative overexpression of ER-alpha and the unresponsiveness to basement membrane regulation found in those malignant cells. Evidence is presented to show the relevance of the cross-talk between different signaling pathways in the constitution of a functional tissue organization and how this integration may be disrupted in the malignant phenotype.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11386/3023365
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