title: Hyperplasia, reduced E-cadherin expression, and developmental arrest in mammary glands oxidatively stressed by loss of mitochondrial superoxide dismutase.
abstract: To investigate the dysregulating effect of excess oxidative stress on mammary gland development, mammary anlage from newborn female mice with normal (+/+) or absent (null, -/-) manganese superoxide dismutase (SOD2) were excised and implanted under the renal capsule of normal host female nude mice with/without concurrent estrogen supplementation. After 30 days the transplanted glands were excised for wholemount, microscopic and immunohistochemical evaluation. In contrast to the normal growth and maturation of transplanted SOD2+/+ glands, SOD2-/- glands showed arrested development, reduced ductal outgrowth and branching, and absent lumen. These hypomorphic SOD2-/- ducts contained hyperplastic epithelium with increased Ki-67 labelling, loss of E-cadherin expression, and disorganized p63 and cytokeratin (K)-14 expressing basal and myoepithelial components. Estrogen treatment failed to upregulate progesterone receptor or normalize development. These findings suggest that excess oxidative stress from loss of SOD2 function can arrest mammary gland maturation and induce hyperplastic epithelium with early premalignant features.
authors.affiliation: Department of Anatomy, University of California, San Francisco, CA 94143, USA.
authors.forename: Hema
authors.initials: H
authors.lastname: Parmar
authors.forename: Simon
authors.initials: S
authors.lastname: Melov
authors.forename: Enrique
authors.initials: E
authors.lastname: Samper
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Ljung
authors.forename: Gerald R
authors.initials: GR
authors.lastname: Cunha
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Benz
mesh_terms: D000818:Animals; D015820:Cadherins / Q000096:biosynthesis*; D002471:Cell Transformation, Neoplastic; D005260:Female; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000201:enzymology* / Q000254:growth & development*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D015820:Cadherins; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase