Characterization of mammary epithelial cell line HC11 using the NIA 15k gene array reveals potential regulators of the undifferentiated and differentiated phenotypes

被引:13
|
作者
Perotti, C. [1 ]
Wiedl, T. [1 ]
Florin, L. [2 ]
Reuter, H. [3 ]
Moffat, S. [1 ]
Silbermann, M. [1 ]
Hahn, M. [3 ]
Angel, P. [2 ]
Shemanko, C. S. [1 ]
机构
[1] Univ Calgary, Dept Biol Sci, Calgary, AB T2N 1N4, Canada
[2] Deutsch Krebsforschungszentrum, Div Signal Transduct & Growth Control, D-69120 Heidelberg, Germany
[3] Deutsch Krebsforschungszentrum, Div Mol Genet, D-69120 Heidelberg, Germany
基金
加拿大自然科学与工程研究理事会;
关键词
Mammary gland; Bone morphogenetic protein receptor; Progenitor; Prolactin; HC11; Gene array; JUNCTIONAL ADHESION MOLECULE; NF-KAPPA-B; BONE MORPHOGENETIC PROTEINS; BREAST-CANCER CELLS; LOOP-HELIX PROTEINS; STEM-CELLS; TIGHT JUNCTIONS; HAIR FOLLICLE; FAMILY-MEMBERS; SELF-RENEWAL;
D O I
10.1016/j.diff.2009.05.003
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Differentiation of undifferentiated mammary epithelial stem and/or progenitor cells results in the production of luminal-ductal and myoepithelial cells in the young animal and upon pregnancy, the production of luminal alveolar cells. A few key regulators of differentiation have been identified, though it is not known yet how these proteins function together to achieve their well-orchestrated products. In an effort to identify regulators of early differentiation, we screened the NIA 15k gene array of 15,247 developmentally expressed genes using mouse mammary epithelial HC11 cells as a model of differentiation. We have confirmed a number of genes preferentially expressed in the undifferentiated cells (Lgals1, Ran, Jam-A and Bmpr1a) and in those induced to undergo differentiation (Id1, Nfkbiz, Trib1, Rps21, Ier3). Using antibodies to the proteins encoded by Lgals1, and Jam-A, we confirmed that their proteins levels were higher in the undifferentiated cells. Although the amounts of bone morphogenetic protein receptor-1A (BMPR1A) protein were present at all stages, we found the activity of its downstream signal transduction pathway, as measured by the presence of phosphorylated-SMAD1, -SMAD5, and -SMAD8, is elevated in undifferentiated cells and decreases in fully differentiated cells. This evidence supports that the BMPR1A pathway functions primarily in undifferentiated mammary epithelial cells. We have identified a number of genes, of known and unknown function, that are candidates for the maintenance of the undifferentiated phenotype and for early regulators of mammary alveolar cell differentiation. (C) 2009 International Society of Differentiation. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:269 / 282
页数:14
相关论文
empty
未找到相关数据