The hallmark of epithelial cells is their polarized morphology and lumen formation. BGP (biliary glycoprotein), a type I transmembrane glycoprotein that is found throughout the gastrointestinal tract and other organs such as the breast, has a polarized expression on the lumenal surface of epithelial cells. We have shown that BGP plays an essential role in the lumen formation of the 'normal"""""""" breast epithelial cell line MCF10F when grown in matrigel, a source of extracellular matrix. Specifically, these cells fail to form a lumen (acinus) when BGP expression is blocked with a BGP anti-sense gene, or when the cells are treated with anti-BGP antibody or with recombinant, soluble BGP. In the case of breast tumor cell lines such as MCF7, which fail to form acini in matrigel and do not express BGP, these cells exhibit massive cell death and occasional acinus formation when transfected with the BGP sense gene and grown in matrigel. In order to delineate the molecular determinants of lumen formation by BGP, we propose to (1) study the defects in MCF7 cells which prevent their reversion to a more """"""""normal"""""""" phenotype, (2) map cytoskeleton interactions with the cytoplasmic domain of BGP, (3) analyze the cis-trans dimer interactions of the BGP ectodomains responsible for lumen formation, and (4) determine the regulation of the BGP gene in both MCF10F and MCF7 cells. In addition, we have found that MCF10F cells produce myoepithelial cells which can be enriched and shown to be BGP negative and capable of induction of CEA (carcinoembryonic antigen), a hallmark of breast cancer cells. We will also study the regulation of the CEA and BGP genes in these cells in order to gain insight into the process of tumorigenesis in breast cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA084202-04
Application #
6633567
Study Section
Metabolic Pathology Study Section (MEP)
Program Officer
Woodhouse, Elizabeth
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
4
Fiscal Year
2003
Total Cost
$411,518
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
027176833
City
Duarte
State
CA
Country
United States
Zip Code
91010
Weng, Chunyue; Nguyen, Tung; Shively, John E (2016) miRNA-342 Regulates CEACAM1-induced Lumen Formation in a Three-dimensional Model of Mammary Gland Morphogenesis. J Biol Chem 291:16777-86
Nguyen, Tung; Shively, John E (2016) Induction of Lumen Formation in a Three-dimensional Model of Mammary Morphogenesis by Transcriptional Regulator ID4: ROLE OF CaMK2D IN THE EPIGENETIC REGULATION OF ID4 GENE EXPRESSION. J Biol Chem 291:16766-76
Nguyen, Tung; Chen, Charng-Jui; Shively, John E (2014) Phosphorylation of CEACAM1 molecule by calmodulin kinase IID in a three-dimensional model of mammary gland lumen formation. J Biol Chem 289:2934-45
Zhang, Hui; Eisenried, Andreas; Zimmermann, Wolfgang et al. (2013) Role of CEACAM1 and CEACAM20 in an in vitro model of prostate morphogenesis. PLoS One 8:e53359
Li, Yun; Shively, John E (2013) CEACAM1 regulates Fas-mediated apoptosis in Jurkat T-cells via its interaction with ?-catenin. Exp Cell Res 319:1061-72
Samineni, Sridhar; Zhang, Zhifang; Shively, John E (2013) Carcinoembryonic antigen-related cell adhesion molecule 1 negatively regulates granulocyte colony-stimulating factor production by breast tumor-associated macrophages that mediate tumor angiogenesis. Int J Cancer 133:394-407
Lu, Rongze; Kujawski, Maciej; Pan, Hao et al. (2012) Tumor angiogenesis mediated by myeloid cells is negatively regulated by CEACAM1. Cancer Res 72:2239-50
Lu, Rongze; Pan, Hao; Shively, John E (2012) CEACAM1 negatively regulates IL-1? production in LPS activated neutrophils by recruiting SHP-1 to a SYK-TLR4-CEACAM1 complex. PLoS Pathog 8:e1002597
Chen, Lanfen; Chen, Zhangguo; Baker, Kristi et al. (2012) The short isoform of the CEACAM1 receptor in intestinal T cells regulates mucosal immunity and homeostasis via Tfh cell induction. Immunity 37:930-46
Li, Lin; Crow, Desiree; Turatti, Fabio et al. (2011) Site-specific conjugation of monodispersed DOTA-PEGn to a thiolated diabody reveals the effect of increasing peg size on kidney clearance and tumor uptake with improved 64-copper PET imaging. Bioconjug Chem 22:709-16

Showing the most recent 10 out of 32 publications