Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is hi...Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.Methods:Immunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.Results:The median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).Conclusion:ANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.展开更多
Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic- and abiotic-induced redox signals. RRTF1 is highly conserved in angio- sperms, but its...Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic- and abiotic-induced redox signals. RRTF1 is highly conserved in angio- sperms, but its physiological role remains elusive. Here we show that inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Transgenic lines overexpressing RRTF1 are impaired in root and shoot development, light sensitive, and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica, which reduces ROS accumulation locally in roots and systemi- cally in shoots, and by antioxidants and ROS inhibitors that scavenge ROS. More than 800 genes were detected in mature leaves and seedlings of transgenic lines overexpressing RRTF1; ∽40% of them have stress-, redox-, ROS-regulated-, ROS-scavenging-, defense-, cell death- and related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box-like sequences in the promoter of RRTFl-responsive genes. Upregulation of RRTF1 by stress stimuli and H202 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenet- ically related RAP2.6, which contains a GCC-box-like sequence in its promoter, but transgenic lines overexpressing RAP2.6 do not accumulate higher ROS levels. RRTF1 also stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the elevated levels of the highly conserved RRTF1 induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals.展开更多
基金supported by funding from Takeda Science Foundation,and JSPS KAKENHI(grant numbers JP19H03793 to Obinata D,JP20K07350 to Takayama K,JP19K09740 to Takahashi S,JP20K07875 to Hara M,and JP20K21667 and JP21H04829 to Inoue S).
文摘Objective:Octamer transcription factor 1(OCT1),a transcription factor that interacts with androgen receptor,is involved in prostate cancer(PCa)progression.The OCT1 target gene,Anillin actin-binding protein(ANLN),is highly expressed in castration-resistant PCa tissue;however,it remains unclear whether ANLN expression in hormone-sensitive PCa tissue could be used as a predictive biomarker for poor prognosis of patients.We aimed to investigate ANLN expression in PCa tissue obtained via radical prostatectomy and its correlation with clinical parameters.Methods:Immunohistochemical staining for ANLN was performed on 86 PCa specimens,followed by evaluation using immunoreactivity(IR)scores.Prognosis was analyzed by the log-rank test using the Kaplan–Meier method to generate a cancer-specific survival curve.The correlations between ANLN IR and clinical parameters as well as OCT1 IR were analyzed using the Chi-squared test.Results:The median IR score was 0 for ANLN.Accordingly,given the low median IR score,an IR score of≥3 was defined as positive.There were 17(19.8%)ANLN-positive cases,and these cases had a significantly poorer prognosis.Multivariate analysis revealed that the Gleason score,pathological tumor and lymph node stages,and positive ANLN expression were significant predictors of poor prognosis.Notably,patients with both positive ANLN and high OCT1 expression had a significantly decreased overall survival(p=0.001).Conclusion:ANLN,which is a OCT1 target gene especially in castration-resistant PCa,is expressed in a small number of hormone-sensitive PCa cases.Both positive ANLN expression and high OCT1 expression are significantly correlated with poor prognosis for PCa patients.
文摘Redox Responsive Transcription Factor1 (RRTF1) in Arabidopsis is rapidly and transiently upregulated by H202, as well as biotic- and abiotic-induced redox signals. RRTF1 is highly conserved in angio- sperms, but its physiological role remains elusive. Here we show that inactivation of RRTF1 restricts and overexpression promotes reactive oxygen species (ROS) accumulation in response to stress. Transgenic lines overexpressing RRTF1 are impaired in root and shoot development, light sensitive, and susceptible to Alternaria brassicae infection. These symptoms are diminished by the beneficial root endophyte Piriformospora indica, which reduces ROS accumulation locally in roots and systemi- cally in shoots, and by antioxidants and ROS inhibitors that scavenge ROS. More than 800 genes were detected in mature leaves and seedlings of transgenic lines overexpressing RRTF1; ∽40% of them have stress-, redox-, ROS-regulated-, ROS-scavenging-, defense-, cell death- and related functions. Bioinformatic analyses and in vitro DNA binding assays demonstrate that RRTF1 binds to GCC-box-like sequences in the promoter of RRTFl-responsive genes. Upregulation of RRTF1 by stress stimuli and H202 requires WRKY18/40/60. RRTF1 is co-regulated with the phylogenet- ically related RAP2.6, which contains a GCC-box-like sequence in its promoter, but transgenic lines overexpressing RAP2.6 do not accumulate higher ROS levels. RRTF1 also stimulates systemic ROS accumulation in distal non-stressed leaves. We conclude that the elevated levels of the highly conserved RRTF1 induce ROS accumulation in response to ROS and ROS-producing abiotic and biotic stress signals.