共查询到10条相似文献,搜索用时 296 毫秒
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Disruption of steroid and prolactin receptor patterning in the mammary gland correlates with a block in lobuloalveolar development 总被引:8,自引:0,他引:8
Grimm SL Seagroves TN Kabotyanski EB Hovey RC Vonderhaar BK Lydon JP Miyoshi K Hennighausen L Ormandy CJ Lee AV Stull MA Wood TL Rosen JM 《Molecular endocrinology (Baltimore, Md.)》2002,16(12):2675-2691
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Naylor MJ Li N Cheung J Lowe ET Lambert E Marlow R Wang P Schatzmann F Wintermantel T Schüetz G Clarke AR Mueller U Hynes NE Streuli CH 《The Journal of cell biology》2005,171(4):717-728
Integrin-mediated adhesion regulates the development and function of a range of tissues; however, little is known about its role in glandular epithelium. To assess the contribution of beta1 integrin, we conditionally deleted its gene in luminal epithelia during different stages of mouse mammary gland development and in cultured primary mammary epithelia. Loss of beta1 integrin in vivo resulted in impaired alveologenesis and lactation. Cultured beta1 integrin-null cells displayed abnormal focal adhesion function and signal transduction and could not form or maintain polarized acini. In vivo, epithelial cells became detached from the extracellular matrix but remained associated with each other and did not undergo overt apoptosis. beta1 integrin-null mammary epithelial cells did not differentiate in response to prolactin stimulation because of defective Stat5 activation. In mice where beta1 integrin was deleted after the initiation of differentiation, fewer defects in alveolar morphology occurred, yet major deficiencies were also observed in milk protein and milk fat production and Stat5 activation, indicating a permissive role for beta1 integrins in prolactin signaling. This study demonstrates that beta1 integrin is critical for the alveolar morphogenesis of a glandular epithelium and for maintenance of its differentiated function. Moreover, it provides genetic evidence for the cooperation between integrin and cytokine signaling pathways. 相似文献
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K D Walton K U Wagner E B Rucker J M Shillingford K Miyoshi L Hennighausen 《Mechanisms of development》2001,109(2):281-293
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Rac1 links integrin-mediated adhesion to the control of lactational differentiation in mammary epithelia 下载免费PDF全文
The expression of tissue-specific genes during mammary gland differentiation relies on the coincidence of two distinct signaling events: the continued engagement of beta1 integrins with the extracellular matrix (ECM) and a hormonal stimulus from prolactin (Prl). How the integrin and Prl receptor (PrlR) systems integrate to regulate milk protein gene synthesis is unknown. In this study, we identify Rac1 as a key link. Dominant-negative Rac1 prevents Prl-induced synthesis of the milk protein beta-casein in primary mammary epithelial cells cultured as three-dimensional acini on basement membrane. Conversely, activated Rac1 rescues the defective beta-casein synthesis that occurs under conditions not normally permissive for mammary differentiation, either in beta1 integrin-null cells or in wild-type cells cultured on collagen. Rac1 is required downstream of integrins for activation of the PrlR/Stat5 signaling cascade. Cdc42 is also necessary for milk protein synthesis but functions via a distinct mechanism to Rac1. This study identifies the integration of signals provided by ECM and hormones as a novel role for Rho family guanosine triphosphatases. 相似文献