Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the mole...Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer,with particular focus on the role of SET Domain Containing 1A(SETD1A)-driven forkhead box A2(FOXA2)as a key regulator of this resistance.Methods:FOXA2 expression and its regulation by SETD1A were assessed via(quantitative polymerase chain reaction),western blotting,transcriptome profiling,and chromatin immunoprecipitation analyses.The effects of FOXA2 on cell proliferation,migration,invasion,and cancer stem cell traits were evaluated using small interfering RNA(siRNA)-mediated silencing.Clinical relevance was examined by analyzing patient datasets and tumor tissue microarrays.Results:FOXA2 expression was significantly elevated in tamoxifen-resistant(TamR)and ERα-negative breast cancer cells compared to that in ERα-positive MCF-7 cells,regardless of tamoxifen treatment or ERαdepletion.Transcriptome and chromatin immunoprecipitation analyses revealed that SETD1A,a histone methyltransferase,directly regulated FOXA2 expression.Functionally,FOXA2 knockdown inhibited the proliferation,migration,invasion,and cancer stem cell properties of TamR cells while restoring tamoxifen sensitivity.High FOXA2 expression was correlated with poor survival and reduced responsiveness to tamoxifen in patients with ER-positive breast cancer.Conclusion:Our findings identified FOXA2 as a key mediator of tamoxifen resistance regulated by SETD1A and suggested that targeting the SETD1A-FOXA2 axis may offer a novel strategy for overcoming endocrine resistance in breast cancer.展开更多
In L-topological spaces,by using the D.-closed set,the concept of remote neighborhood for a point is generalized,the layer closure of an L-subset is defined,and the layer convergence of a net is established.
SET(patient SE translocation,SET)基因,又名模板活化因子-1(template activating factor,TAF-1),因首次鉴定于伴有该基因染色体异位的未分化型白血病患者SE而命名。SET蛋白具有多种生物功能,可以通过影响组蛋白乙酰化、转录调节、核...SET(patient SE translocation,SET)基因,又名模板活化因子-1(template activating factor,TAF-1),因首次鉴定于伴有该基因染色体异位的未分化型白血病患者SE而命名。SET蛋白具有多种生物功能,可以通过影响组蛋白乙酰化、转录调节、核小体装配等,参与基因表达调控、翻译后修饰、细胞凋亡等多个生物过程,是重要的细胞因子。一些消化和血液系统肿瘤、生殖与神经系统的疾病伴有SET表达或亚细胞定位异常,提示SET与这些疾病的发生发展相关。SET基因转录剪切产生TAF-Iα和SET/TAF-Iβ2个亚型,而SET/TAF-Iβ可能发挥着SET蛋白的主要生物学作用。展开更多
Objective To evaluate the ability of showing the pancreatlc dlseases on varlous MRI sequences. Methods Eighty-four subJects included 5O normal individuals and 34 patlents(22 patients investlgated for pancreatic neopIa...Objective To evaluate the ability of showing the pancreatlc dlseases on varlous MRI sequences. Methods Eighty-four subJects included 5O normal individuals and 34 patlents(22 patients investlgated for pancreatic neopIasia and 12 pancreatitis) were presented. The MR protocol inc1uded conventional SE T1WI, FSE T2WI, Pre-and post-contrast T,-weighted fat-suppressed and GRE imaging. ResuIts The best diagnostic information was provided by Tl-weighted fatsuppressed imaging before and after gadolinium enhancement on 27 of 34 cases with abnorm8I pancreas, followed by immediately postcontrast GRE images. Precontrast GRE imaging better showed the features of acute pancreatitis. FSE T2WI obviously exhibited lsiet cell tumor and metastases of Iiver from pancreatic adenocarcinoma. Conclusion The standard MR protocol included T1-weigkted fat-suppressed image and dynamic GRE imaging.展开更多
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF),funded by the Ministry of Education(RS-2023-00248378 and NRF-2020R1A6A1A03043708).
文摘Objectives:Tamoxifen is a key drug that provides endocrine therapy for estrogen receptor(ER)α-positive breast cancer;however,resistance remains a significant clinical challenge.This study aims to investigate the molecular mechanisms of tamoxifen resistance in ERα-positive breast cancer,with particular focus on the role of SET Domain Containing 1A(SETD1A)-driven forkhead box A2(FOXA2)as a key regulator of this resistance.Methods:FOXA2 expression and its regulation by SETD1A were assessed via(quantitative polymerase chain reaction),western blotting,transcriptome profiling,and chromatin immunoprecipitation analyses.The effects of FOXA2 on cell proliferation,migration,invasion,and cancer stem cell traits were evaluated using small interfering RNA(siRNA)-mediated silencing.Clinical relevance was examined by analyzing patient datasets and tumor tissue microarrays.Results:FOXA2 expression was significantly elevated in tamoxifen-resistant(TamR)and ERα-negative breast cancer cells compared to that in ERα-positive MCF-7 cells,regardless of tamoxifen treatment or ERαdepletion.Transcriptome and chromatin immunoprecipitation analyses revealed that SETD1A,a histone methyltransferase,directly regulated FOXA2 expression.Functionally,FOXA2 knockdown inhibited the proliferation,migration,invasion,and cancer stem cell properties of TamR cells while restoring tamoxifen sensitivity.High FOXA2 expression was correlated with poor survival and reduced responsiveness to tamoxifen in patients with ER-positive breast cancer.Conclusion:Our findings identified FOXA2 as a key mediator of tamoxifen resistance regulated by SETD1A and suggested that targeting the SETD1A-FOXA2 axis may offer a novel strategy for overcoming endocrine resistance in breast cancer.
文摘In L-topological spaces,by using the D.-closed set,the concept of remote neighborhood for a point is generalized,the layer closure of an L-subset is defined,and the layer convergence of a net is established.
文摘SET(patient SE translocation,SET)基因,又名模板活化因子-1(template activating factor,TAF-1),因首次鉴定于伴有该基因染色体异位的未分化型白血病患者SE而命名。SET蛋白具有多种生物功能,可以通过影响组蛋白乙酰化、转录调节、核小体装配等,参与基因表达调控、翻译后修饰、细胞凋亡等多个生物过程,是重要的细胞因子。一些消化和血液系统肿瘤、生殖与神经系统的疾病伴有SET表达或亚细胞定位异常,提示SET与这些疾病的发生发展相关。SET基因转录剪切产生TAF-Iα和SET/TAF-Iβ2个亚型,而SET/TAF-Iβ可能发挥着SET蛋白的主要生物学作用。
文摘Objective To evaluate the ability of showing the pancreatlc dlseases on varlous MRI sequences. Methods Eighty-four subJects included 5O normal individuals and 34 patlents(22 patients investlgated for pancreatic neopIasia and 12 pancreatitis) were presented. The MR protocol inc1uded conventional SE T1WI, FSE T2WI, Pre-and post-contrast T,-weighted fat-suppressed and GRE imaging. ResuIts The best diagnostic information was provided by Tl-weighted fatsuppressed imaging before and after gadolinium enhancement on 27 of 34 cases with abnorm8I pancreas, followed by immediately postcontrast GRE images. Precontrast GRE imaging better showed the features of acute pancreatitis. FSE T2WI obviously exhibited lsiet cell tumor and metastases of Iiver from pancreatic adenocarcinoma. Conclusion The standard MR protocol included T1-weigkted fat-suppressed image and dynamic GRE imaging.
