Estrogen receptor beta suppresses the androgen receptor oncogenic effects in triple-negative breast cancer / 中华医学杂志(英文版)

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 ERβ and 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 ERβ positive and AR positive. We further demonstrated the pro-tumoral effects of AR on TNBC cells, however, the oncogenic biology was significantly suppressed when ERβ transfection 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 ERβ interacted with AR thus impeding the AR-mediated NECTIN4 transcription which promoted epithelial-mesenchymal transition in tumor progression.@*CONCLUSIONS@#This study suggests that ERβ functions 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.

Effects of prostaglandin E1 on the levels of myocardium NF-κB and plasma TNF-α in patients underwent heart valve replacement / 重庆医学

Objective To investigate the effects of prostaglandin E1 (PGE1) on the levels of myocardium nuclear factor‐κB (NF‐κB) and plasma tumor necrosis factor‐α (TNF‐α) in patients underwent heart valve replacement .Methods Forty ASA Ⅱ orⅢ degree patients (NYHA Ⅱ or Ⅲ degree) ,aged 32 to 67 years with body mass index of 17 to 28 kg/m2 ,underwent heart valve replacement ,were randomly divided into 2 groups (n=20):control group (group C) and PGE1 group (group P) .After induction of anesthesia ,PGE1 20 ng · kg -1 · min-1 was infused intravenously in group P ,while the equivalent volume of normal saline was giv‐en in group C ,and the infusion was completed at the end of operation .Arterial blood samples were collected at the time of before cardiopulmonary bypass (T0 ,baseline) ,30 min after the begin of cardiopulmonary bypass (T1 ) ,the end of cardiopulmonary bypass (T2 ) ,and 12 h(T3 ) ,24 h(T4 ) after the end of cardiopulmonary bypass .Myocardial specimens were obtained from right auricular appendage at T0 and T2 for microscopic examination and determination the activity of NF‐κB .Results The plasma mass concentra‐tions of TNF‐αwas significantly lower (P<0 .05) at T1 to T4 ,while the myocardial histopathological damage was lighter and the activity of NF‐κb significantly attenuated (P<0 .05) at T2 in group P than that in group C .Conclusion PGE1 can attenuate myo‐cardial injury in patients underwent heart valve replacement ,the mechanism is related to inhibit the activity of myocardium NF‐κB and decrease the plasma mass concentrations of TNF‐α.