title: Malignant mammary cells acquire independence from extracellular context for regulation of estrogen receptor alpha.
abstract: Interactions between luminal epithelial cells and their surrounding microenvironment govern the normal development and function of the mammary gland. Alterations of these interactions can induce abnormal intracellular 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) alpha expression, and that this response could be interfered with by disrupting cell-extracellular matrix adhesion. Here we use phenotypically normal mammary epithelial SCp2 cells to dissect the promoter region of the ERalpha that is involved in the selective response to basement membrane. We also analyze the alteration of this response in SCg6 cells, a malignant cell line that shares a common lineage with the SCp2 cells, to provide insight into the relative overexpression of ERalpha 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.
authors.affiliation: Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, and Dipartimento di Patologia generale, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Novaro
authors.forename: Derek C
authors.initials: DC
authors.lastname: Radisky
authors.forename: Nancy E
authors.initials: NE
authors.lastname: Ramos Castro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Weisz
authors.forename: Mina J
authors.initials: MJ
authors.lastname: Bissell
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008321:Mammary Glands, Animal / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008957:Models, Genetic; D010641:Phenotype; D011401:Promoter Regions, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic
chemical_list: D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen