前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与...前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与禽副黏病毒NDV感染的感染过程[1]。为了验证鸡源Nectin4(chNectin4)和鸡源SLAM(chSLAM)在NDV感染中的作用,本研究构建了分别稳定表达chNectin4和chSLAM的BHK21细胞系。感染实验结果显示,稳定表达chNectin4和chSLAM细胞系在接种NDV La Sota株后12 h和24 h NP mRNA水平显著高于亲本细胞,表明chNectin4和chSLAM有助于促进NDV在BHK21细胞系中的增殖,其中chNectin4的促NDV增殖作用更加明显。本研究为进一步研究鸡Nectin4和SLAM在NDV感染中的作用以及NDV疫苗的研究奠定了基础。展开更多
Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target ...Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)TNBC.However,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits.This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC tissues.Then,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in TNBC.Chromatin immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of AR.Results:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR positive.We further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative TNBC.Mechanistically,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.Conclusions:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation.Therefore,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.展开更多
文摘前期研究发现,信号淋巴细胞活化分子(signaling lymphocyte activation molecule,SLAM or CD150)和脊髓灰质炎病毒受体相关蛋白4(poliovirus receptor-related protein 4,PVRL4 or Nectin4)是麻疹病毒属副黏病毒的主要细胞受体,也参与禽副黏病毒NDV感染的感染过程[1]。为了验证鸡源Nectin4(chNectin4)和鸡源SLAM(chSLAM)在NDV感染中的作用,本研究构建了分别稳定表达chNectin4和chSLAM的BHK21细胞系。感染实验结果显示,稳定表达chNectin4和chSLAM细胞系在接种NDV La Sota株后12 h和24 h NP mRNA水平显著高于亲本细胞,表明chNectin4和chSLAM有助于促进NDV在BHK21细胞系中的增殖,其中chNectin4的促NDV增殖作用更加明显。本研究为进一步研究鸡Nectin4和SLAM在NDV感染中的作用以及NDV疫苗的研究奠定了基础。
基金supported by grants from the Key International Cooperation of the National Natural Science Foundation of China(No.81920108029)the Key Foundation for Social Development Project of the Jiangsu Province,China(No.BE2021741)Youth Fund of the National Natural Science Foundation of China(No.82002783)
文摘Background:Triple-negative breast cancer(TNBC)is an aggressive type of breast cancer associated with poor prognosis and limited treatment options.The androgen receptor(AR)has emerged as a potential therapeutic target for luminal androgen receptor(LAR)TNBC.However,multiple studies have claimed that anti-androgen therapy for AR-positive TNBC only has limited clinical benefits.This study aimed to investigate the role of AR in TNBC and its detailed mechanism.Methods:Immunohistochemistry and TNBC tissue sections were applied to investigate AR and nectin cell adhesion molecule 4(NECTIN4)expression in TNBC tissues.Then,in vitro and in vivo assays were used to explore the function of AR and estrogen receptor beta(ERβ)in TNBC.Chromatin immunoprecipitation sequencing(ChIP-seq),co-immunoprecipitation(co-IP),molecular docking method,and luciferase reporter assay were performed to identify key molecules that affect the function of AR.Results:Based on the TNBC tissue array analysis,we revealed that ERβand AR were positive in 21.92%(32/146)and 24.66%(36/146)of 146 TNBC samples,respectively,and about 13.70%(20/146)of TNBC patients were ERβpositive and AR positive.We further demonstrated the pro-tumoral effects of AR on TNBC cells,however,the oncogenic biology was significantly suppressed when ERβtransfection in LAR TNBC cell lines but not in AR-negative TNBC.Mechanistically,we identified that NECTIN4 promoter–42 bp to–28 bp was an AR response element,and that ERβinteracted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial–mesenchymal transition in tumor progression.Conclusions:This study suggests that ERβfunctions as a suppressor mediating the effect of AR in TNBC prognosis and cell proliferation.Therefore,our current research facilitates a better understanding of the role and mechanisms of AR in TNBC carcinogenesis.
