The Role of Nuclear Corepressor-2-mediated Epigenetic Regulation on Fibronectin Expression in MammaryBranching Morphogenesis

• Main Authors: Ming-Sheng Liu, 劉銘聖
• Other Authors: Jung-Yie Kao
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/23851098428392186251

碩士 === 國立中興大學 === 生命科學院碩士在職專班 === 98 === Branching morphogenesis of mammary glands requires site-specific alterations in cell-cell and cell-matrix adhesions; However, the molecular mechanisms underlying this developmental process remain less understood. Using immunohistochemical and bioengineering approaches, we show here that nuclear receptor co-repressor 2 (N-CoR2) plays a crucial role in regulating mammary branching morphogenesis. In normal human breast epithelium, N-CoR2 displays a considerable inter-regional expressional heterogeneity with its levels higher in mammary acini than the adjacent ductules. Using three-dimensional mammary morphogenesis models, we showed that RNA-interference-mediated knockdown of endogenous N-CoR2 in mammary acini led to a dramatic upregulation of the extracellular protein fibronectin (FN) accompanied with reduced E-cadherin expression, which were functionally linked to the initiation of branching. In line with these in vitro findings, we further provided compelling evidence for the role of N-CoR2-mediated regulation on FN expression during the developmental process of mouse mammary glands. Specifically, N-CoR2 is predominantly expressed in the luminal epithelial cells of the outermost layer of the developing terminal end buds (TEBs) and its expression abruptly declines at the bifurcation sites. Coincidental with the site-specific changes of N-CoR2 expression, the luminal epithelial cells accumulate pericellular FN at the bifurcation sites. Together, our findings suggest a novel paradigm of an epigenetic regulation for mammary branching morphogenesis mediated by N-CoR2.