Hugl1 and Hugl2 in mammary epithelial cells: polarity, proliferation, and differentiation

Autor: Atlantis Dawn Russ, Daniela C. Zarnescu, Joyce A. Schroeder, Jeanne M. V. Louderbough
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Cellular differentiation
Fluorescent Antibody Technique
Tetrazolium Salts
lcsh:Medicine
Cell polarity
Molecular Cell Biology
Breast Tumors
Basic Cancer Research
Image Processing
Computer-Assisted
lcsh:Science
Epithelial polarity
0303 health sciences
Multidisciplinary
030302 biochemistry & molecular biology
Obstetrics and Gynecology
Cell Polarity
Cell Differentiation
Cellular Structures
Cell biology
Drug Combinations
medicine.anatomical_structure
Oncology
Gene Knockdown Techniques
Medicine
Membranes and Sorting
Female
Proteoglycans
Collagen
Cellular Types
Research Article
Blotting
Western
Biology
Cell Growth
03 medical and health sciences
Cell Line
Tumor
Breast Cancer
medicine
Cell Adhesion
Humans
Mammary Glands
Human
030304 developmental biology
Cell Proliferation
Cell Nucleus
Matrigel
Cell growth
lcsh:R
Myoepithelial cell
Cancers and Neoplasms
Epithelial Cells
Epithelium
Cytoskeletal Proteins
Thiazoles
Gene Expression Regulation
Microscopy
Fluorescence
Cell culture
lcsh:Q
Laminin
Zdroj: PLoS ONE, Vol 7, Iss 10, p e47734 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: Loss of epithelial polarity is described as a hallmark of epithelial cancer. To determine the role of Hugl1 and Hugl2 expression in the breast, we investigated their localization in human mammary duct tissue and the effects of expression modulation in normal and cancer cell lines on polarity, proliferation and differentiation. Expression of Hugl1 and Hugl2 was silenced in both MCF10A cells and Human Mammary Epithelial Cells and cell lines were grown in 2-D on plastic and in 3-D in Matrigel to form acini. Cells in monolayer were compared for proliferative and phenotypic changes while acini were examined for differences in size, ability to form a hollow lumen, nuclear size and shape, and localization of key domain-specific proteins as a measure of polarity. We detected overlapping but distinct localization of Hugl1 and Hugl2 in the human mammary gland, with Hugl1 expressed in both luminal and myoepithelium and Hugl2 largely restricted to myoepithelium. On a plastic surface, loss of Hugl1 or Hugl2 in normal epithelium induced a mesenchymal phenotype, and these cells formed large cellular masses when grown in Matrigel. In addition, loss of Hugl1 or Hugl2 expression in MCF10A cells resulted in increased proliferation on Matrigel, while gain of Hugl1 expression in tumor cells suppressed proliferation. Loss of polarity was also observed with knockdown of either Hugl1 or Hugl2, with cells growing in Matrigel appearing as a multilayered epithelium, with randomly oriented Golgi and multiple enlarged nuclei. Furthermore, Hugl1 knock down resulted in a loss of membrane identity and the development of cellular asymmetries in Human Mammary Epithelial Cells. Overall, these data demonstrate an essential role for both Hugl1 and Hugl2 in the maintenance of breast epithelial polarity and differentiated cell morphology, as well as growth control.
Databáze: OpenAIRE
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