RHBDF1通过与Par6a结合破坏乳腺腺泡顶-底部极性的形成
首发时间:2017-05-12
摘要:目的:研究RHBDF1在乳腺腺泡顶-底部极性的形成中的作用。方法:在体外和体内采用乳腺细胞3D培养和Matrigel Plug的方法模拟乳腺腺泡发生,用免疫荧光、Western Blot和免疫共沉淀的方法检测腺泡发生过程中RHBDF1对极性标识物GM130和Laminin-5及极性复合物蛋白Par6、Par3和Rac1/Cdc42的表达位置和相互作用关系的影响;用免疫荧光观察RHBDF1在小鼠体内对乳腺腺泡顶-底部极性发生的影响。结果:RHBDF1通过与Par6a结合,进而影响Rac1/Cdc42-Par6-Par3极性发生复合物的形成,从而破坏乳腺腺泡正常顶-底部极性的形成。结论:过表达RHBDF1能够破坏乳腺腺泡正常顶-底部极性的发生,其极有可能成为治疗乳腺癌的新靶点。
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RHBDF1 Interacts with Par6a to Impair Apicobasal Polarity of Mammary Acini during Morphogenesis
Abstract:Objective: To investigate the role of RHBDF1 overexpression in MCF-10A to form apicobasal polarity of mammary acini in 3-D cultures. Methods: Immunostaining, western blot, and Co-IP were employed to detect the location of apicobasal polarity marker GM130 and Laminin-5, and the interaction of Par6, Par3, and Rac1/Cdc42 with RHBDF1 in mammary acini during morphogenesis by 3D culture. In addition, immunostaining was employed to examine the apicobasal polarity marker of mammary acini during morphogenesis in NOD/SCID mice by Matrigel plug. Results: RHBDF1 can interact with Par6a to perturb the Rac1/Cdc42-Par6-Par3 complex formation of mammary acini to impair the apicobasal polarity of mammary acini in vitro and in vivo. Conclusion: RHBDF1 overexpression in MCF-10A can destroy apicobasal polarity formation of mammary acini, and it may be as a novel target in the treatment of breast cancer.
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No.4732300119948614****
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