The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than ha...The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)展开更多
The androgen receptor(AR)remains a key driver of prostate cancer(PCa)progression,even in the advanced castrate-resistant stage,where testicular androgens are absent.It is therefore of critical importance to understand...The androgen receptor(AR)remains a key driver of prostate cancer(PCa)progression,even in the advanced castrate-resistant stage,where testicular androgens are absent.It is therefore of critical importance to understand the molecular mechanisms governing its activity and regulation during prostate tumourigenesis.MicroRNAs(miRs)are small w22 nt noncoding RNAs that regulate target gene,often through association with 30 untranslated regions(30UTRs)of transcripts.They display dysregulation during cancer progression,can function as oncogenes or tumour suppressors,and are increasingly recognised as targets or regulators of hormonal action.Thus,understanding factors which modulate miRs synthesis is essential.There is increasing evidence for complex and dynamic bi-directional cross-talk between the multi-step miR biogenesis cascade and the AR signalling axis in PCa.This review summarises the wealth of mechanisms by which miRs are regulated by AR,and conversely,how miRs impact AR’s transcriptional activity,including that of AR splice variants.In addition,we assess the implications of the convergence of these pathways on the clinical employment of miRs as PCa biomarkers and therapeutic targets.展开更多
Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by andr...Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaP as-AR . LNCaP cells containing empty vector pLXSN served as LNCaP Neo . LNCaP and LNCaP Neo were taken as controls In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively Results Growth of LNCaP as-AR was inhibited significantly ( P <0 05) compared with that of LNCaP and LNCaP Neo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively No difference was seen between LNCaP and LNCaP Neo ( P >0 05) Microscopic observation showed that LNCaP and LNCaP Neo cells grew well, but only few LNCaP as-AR cells were alive Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer展开更多
Aim:To investigate the involvement of the prostate androgen-regulated(PAR)gene in the androgen receptor(AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer(PCa)cells.Methods:The d...Aim:To investigate the involvement of the prostate androgen-regulated(PAR)gene in the androgen receptor(AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer(PCa)cells.Methods:The difference in PAR expression between LNCaP and PC3 cells was detected by reverse transcription-polymerase chain reaction(RT-PCR).Androgen and anti-androgen effects on PAR expression were evaluated by RT-PCR in LNCaP,PC3 cells and PC3 cells stably transfected with vector containing wild-type AR.To determine the importance of PAR in the malignant proliferation of androgen-independent PCa cells,we used small interfering RNA(siRNA)transfection to knock down the expression of the gene in PC3 cells.The changes in the malignant phenotype of PCa cells after transfection were analyzed by cell count,colony formation in soft agar and flow cytometry.Results:PAR expression was 3-fold higher in PC3 cells than that in LNCaP cells.Dihydrotestosterone(DHT)regulated PAR mRNA expression in LNCaP cells and the effect was inhibited by the AR antagonist,flutamide.By contrast,DHT did not affect PAR expression in PC3 cells.The reintroduction of AR into PC3 cells by stable transfection restored the androgen effect on PAR upregulation. After the knockdown of the PAR gene by siRNA,PC3 cells exhibited a reversal of the malignant phenotype.Conclusion: Because of the possibility that PAR is downstream from the AR,and because of its contribution to malignant proliferation in androgen-independent PCa cells,the gene could be a potential therapeutic target for androgen-independent PCa with AR signaling pathway alteration.(Asian J Andro12006 Jul;8:455-462)展开更多
目的探讨前列腺癌相关长链非编码RNA(prostate cancer related long non-coding RNA,PCRL)在前列腺癌中的表达情况及其潜在的生物学功能。方法采用qRT-PCR检测PCRL在前列腺癌组织、癌旁组织及其他组织中的表达,同法检测并比较PCRL在雄...目的探讨前列腺癌相关长链非编码RNA(prostate cancer related long non-coding RNA,PCRL)在前列腺癌中的表达情况及其潜在的生物学功能。方法采用qRT-PCR检测PCRL在前列腺癌组织、癌旁组织及其他组织中的表达,同法检测并比较PCRL在雄激素依赖(LNCaP-AD)与雄激素非依赖(LNCaP-AI)前列腺癌细胞和正常前列腺上皮细胞(RWPE-1)中的表达差异。以siRNA干扰PCRL后,采用qRT-PCR方法检测LNCaP-AI细胞和LNCaP-AD细胞中雄激素受体的表达变化。结果 PCRL在前列腺及前列腺癌组织中特异高表达,LNCaP-AI细胞中PCRL水平高于LNCaP-AD细胞和RWPE-1细胞。干扰PCRL后LNCaP-AI细胞和LNCaP-AD细胞中雄激素受体的表达量上升(前者P<0.000 1)。结论在前列腺癌中特异高表达的PCRL与前列腺癌的进展有关,PCRL和雄激素受体之间可能存在一定的调控关系。展开更多
文摘The growth of prostate cancer is sensitive to androgen, and hormonal therapy has been used for treatment of ad-vanced cancer. About 80% of prostate cancers initially respond to hormonal therapy, howerver, more than half of the re-sponders gradually become resistant to this therapy. Changes in tumors from an androgen-responsive to an androgen-unre-sponsive state have been widely discussed. Since androgen action is mediated by androgen receptor (AR), abnormalitiesof AR is believed to play an important role of the loss of androgen responsiveness in prostate cancer. This article focusedon the role of AR in the progression of prostate cancer. (Asian J Androl 1999 Sep; 1: 81-85)
基金The authors gratefully acknowledge research funding from the Prostate Cancer Foundation,Prostate Cancer UK,The Rosetrees Trust and Imperial College London.
文摘The androgen receptor(AR)remains a key driver of prostate cancer(PCa)progression,even in the advanced castrate-resistant stage,where testicular androgens are absent.It is therefore of critical importance to understand the molecular mechanisms governing its activity and regulation during prostate tumourigenesis.MicroRNAs(miRs)are small w22 nt noncoding RNAs that regulate target gene,often through association with 30 untranslated regions(30UTRs)of transcripts.They display dysregulation during cancer progression,can function as oncogenes or tumour suppressors,and are increasingly recognised as targets or regulators of hormonal action.Thus,understanding factors which modulate miRs synthesis is essential.There is increasing evidence for complex and dynamic bi-directional cross-talk between the multi-step miR biogenesis cascade and the AR signalling axis in PCa.This review summarises the wealth of mechanisms by which miRs are regulated by AR,and conversely,how miRs impact AR’s transcriptional activity,including that of AR splice variants.In addition,we assess the implications of the convergence of these pathways on the clinical employment of miRs as PCa biomarkers and therapeutic targets.
基金ThisworkwassupportedbyagrantfromtheNationalNaturalScienceFoundationofChina (No 3 9770 740 )
文摘Background The failure of endocrine treatment for advanced prostate cancer might be related to aberrant activation of androgen receptor (AR) Prostate cancer cell line LNCaP contains AR that can be activated by androgen, estrogen and progesterone This study was set to investigate the effects of antisense AR RNA on growth of LNCaP cultured in medium containing varied concentrations of R1881, 17β-estradiol, and progesterone, respectively Methods LNCaP cells transfected with antisense AR RNA retroviral vector pL-AR-SN were designated as LNCaP as-AR . LNCaP cells containing empty vector pLXSN served as LNCaP Neo . LNCaP and LNCaP Neo were taken as controls In vitro cell growth assay, proliferative cells of LNCaP and tranfected LNCaPs were counted by typan staining when they cultured with synthetic androgen R1881, 17β-estradiol, and progesterone, respectively Results Growth of LNCaP as-AR was inhibited significantly ( P <0 05) compared with that of LNCaP and LNCaP Neo at 1 nmol/L R1881, 10 nmol/L 17β-estradiol, and 1 nmol/L progesterone, respectively No difference was seen between LNCaP and LNCaP Neo ( P >0 05) Microscopic observation showed that LNCaP and LNCaP Neo cells grew well, but only few LNCaP as-AR cells were alive Conclusions Our observations indicate that antisense AR RNA retroviral vector pL-AR-SN could change androgen-independent characteristics of LNCaP cells, which might shed some novel insights into the treatment of androgen-independent prostate cancer
文摘Aim:To investigate the involvement of the prostate androgen-regulated(PAR)gene in the androgen receptor(AR) signaling pathway and the malignant phenotype of androgen-independent prostate cancer(PCa)cells.Methods:The difference in PAR expression between LNCaP and PC3 cells was detected by reverse transcription-polymerase chain reaction(RT-PCR).Androgen and anti-androgen effects on PAR expression were evaluated by RT-PCR in LNCaP,PC3 cells and PC3 cells stably transfected with vector containing wild-type AR.To determine the importance of PAR in the malignant proliferation of androgen-independent PCa cells,we used small interfering RNA(siRNA)transfection to knock down the expression of the gene in PC3 cells.The changes in the malignant phenotype of PCa cells after transfection were analyzed by cell count,colony formation in soft agar and flow cytometry.Results:PAR expression was 3-fold higher in PC3 cells than that in LNCaP cells.Dihydrotestosterone(DHT)regulated PAR mRNA expression in LNCaP cells and the effect was inhibited by the AR antagonist,flutamide.By contrast,DHT did not affect PAR expression in PC3 cells.The reintroduction of AR into PC3 cells by stable transfection restored the androgen effect on PAR upregulation. After the knockdown of the PAR gene by siRNA,PC3 cells exhibited a reversal of the malignant phenotype.Conclusion: Because of the possibility that PAR is downstream from the AR,and because of its contribution to malignant proliferation in androgen-independent PCa cells,the gene could be a potential therapeutic target for androgen-independent PCa with AR signaling pathway alteration.(Asian J Andro12006 Jul;8:455-462)
文摘目的探讨前列腺癌相关长链非编码RNA(prostate cancer related long non-coding RNA,PCRL)在前列腺癌中的表达情况及其潜在的生物学功能。方法采用qRT-PCR检测PCRL在前列腺癌组织、癌旁组织及其他组织中的表达,同法检测并比较PCRL在雄激素依赖(LNCaP-AD)与雄激素非依赖(LNCaP-AI)前列腺癌细胞和正常前列腺上皮细胞(RWPE-1)中的表达差异。以siRNA干扰PCRL后,采用qRT-PCR方法检测LNCaP-AI细胞和LNCaP-AD细胞中雄激素受体的表达变化。结果 PCRL在前列腺及前列腺癌组织中特异高表达,LNCaP-AI细胞中PCRL水平高于LNCaP-AD细胞和RWPE-1细胞。干扰PCRL后LNCaP-AI细胞和LNCaP-AD细胞中雄激素受体的表达量上升(前者P<0.000 1)。结论在前列腺癌中特异高表达的PCRL与前列腺癌的进展有关,PCRL和雄激素受体之间可能存在一定的调控关系。
