Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer develop...Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.展开更多
When exposing to environmental stress or internal damage,such as genotoxic stress,oxidative stress,and heat stress,cells produce a series of adaptive responses called cellular stress responses[1].The major proteins in...When exposing to environmental stress or internal damage,such as genotoxic stress,oxidative stress,and heat stress,cells produce a series of adaptive responses called cellular stress responses[1].The major proteins involved in cellular stress are heat shock proteins(HSPs).HSPs remain in a low expression level and display a diffused distribution in the nucleoplasm and cytoplasm under basal conditions.In response to various stress conditions。展开更多
基金supported by the National Key R&D Program of China(2016YFE0129200)the National Natural Science Foundation of China(31571321,31171428)the Institute of the Fundamental Research Funds of Shandong University(2015JC036)
文摘Polycomblike2(PCL2) is a well-known component of polycomb repressive complex 2(PRC2) and plays important roles in H3 K27 methylation and homeotic gene silencing.However,the involvement of PCL2 in breast cancer development remains unclear.Here,we established PCL2 as a tumor suppressor gene in breast cancer.Expression level of PCL2 was significantly downregulated in breast cancer tissue samples observed at different TNM stages.Ectopic expression of PCL2 could significantly inhibit cell proliferation and promoted apoptosis.PCL2 also remarkably elevated levels of p53 and its targets by increasing p53 stability.Mechanistically,PCL2 protected p53 proteins from MDM2-mediated ubiquitination and degradation by sequestering MDM2 into the nucleolus.Overexpression of PCL2 also suppressed migration and invasion by inhibiting epithelial-mesenchymal transition.PCL2 expression was correlated with Ecadherin expression and was inversely correlated with vimentin expression.Furthermore,PCL2 knockdown could attenuate anti-tumor effect of MLN4924.Taken together,our findings indicated that PCL2 played a tumor suppressor role in development and progression of breast cancer and may be a prognostic and predictive marker for breast cancer.
基金supported by the National Natural Science Foundation of China (31571321, 31171428)the National Key Research and Develepment Program of China (2016YFE0129200)+1 种基金the Institute of the Fundamental Research Funds of Shandong University (2015JC036)the Open Projects of State Key Laboratory of Molecular Oncology (SKL-KF-2017-17)
文摘When exposing to environmental stress or internal damage,such as genotoxic stress,oxidative stress,and heat stress,cells produce a series of adaptive responses called cellular stress responses[1].The major proteins involved in cellular stress are heat shock proteins(HSPs).HSPs remain in a low expression level and display a diffused distribution in the nucleoplasm and cytoplasm under basal conditions.In response to various stress conditions。