Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaPcell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different exp...Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaPcell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different expres-sions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. Results; Data were obtained from threeprostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5,6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the secondspecimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressedall the three AR isoforms. Binding of ~3H-dihydrotestosterone (~3H-DHT) to these three isoforms was inhibited by the ad-dition of 100-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. Conclu-sion : The expression of AR isoforms is different in different prostate cancer tissues, which may be related to the dif-ference in the effect of anti-androgen therapy in different patients. (Asian J Androl 2001 Sep; 3: 223 - 225)展开更多
Aim: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatictissues. Methods: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained...Aim: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatictissues. Methods: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from pa-tients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPHspecimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4℃, the tissues were ex-amined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. Results:From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In humanBPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 iso-fora at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 iso-forms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at differ-ent combinations. Binding of ~3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-foldexcess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. Conclusion: AR isoforms aredifferent in different patients. Although their genesis is not clear, the therapeutic implication of the present observationappears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.(Asian J Androl 2000 Dec; 2: 307-310)展开更多
目的观察补骨脂素对体外培养的前列腺癌LNCa P-AD细胞增殖的抑制作用,并探讨补骨脂素抑制前列腺癌的作用机制。方法体外培养前列腺癌LNCa P-AD细胞,加入不同浓度的补骨脂素,CCK-8法检测细胞增殖抑制率、实时荧光定量PCR检测细胞AR m RN...目的观察补骨脂素对体外培养的前列腺癌LNCa P-AD细胞增殖的抑制作用,并探讨补骨脂素抑制前列腺癌的作用机制。方法体外培养前列腺癌LNCa P-AD细胞,加入不同浓度的补骨脂素,CCK-8法检测细胞增殖抑制率、实时荧光定量PCR检测细胞AR m RNA的表达、Western Blot检测细胞PCNA和AR蛋白表达。采用单因素方差分析进行组间均数比较。结果与对照组相比,30、50、100μg/ml补骨脂素组LNCa P-AD细胞存活率均明显下降(P<0.05),补骨脂素对LNCa P-AD细胞增殖的抑制作用呈浓度-时间依赖性。实时荧光定量PCR检测结果显示,与对照组(1.00±0.00)相比,30μg/ml组AR m RNA表达上调(1.63±0.04,t=17.72,P<0.01),50μg/ml组AR m RNA表达无明显变化(0.98±0.04,t=0.66,P=0.53)、而100μg/ml组的AR m RNA表达则明显降低(0.46±0.07,t=15.18,P<0.01)。Western blot法检测结果显示,30μg/ml、50μg/ml、100μg/ml的补骨脂素干预48 h后,LNCa P-AD细胞PCNA蛋白表达均显著降低(11.88±0.21 vs 10.61±0.17 vs 6.62±0.13 vs 2.71±0.43,F=68.53,P<0.01)。100μg/ml的补骨脂素可明显降低LNCa P-AD细胞AR蛋白的表达水平(0.43±0.06 vs 0.87±0.04,t=6.04,P<0.01)。结论补骨脂素能在体外抑制前列腺癌LNCa P-AD细胞增殖,且呈剂量-时间依赖性,其机制可能与其下调LNCa P-AD细胞PCNA表达和影响AR表达有关。展开更多
前列腺癌的发病率逐年上升,大多数中晚期前列腺癌患者最终都会进展至去势抵抗性前列腺癌(castrationresistant prostate cancer,CRPC)。CRPC患者的中位生存期往往小于20个月,对于这部分患者的治疗方法十分有限。由于CRPC发生和发展机制...前列腺癌的发病率逐年上升,大多数中晚期前列腺癌患者最终都会进展至去势抵抗性前列腺癌(castrationresistant prostate cancer,CRPC)。CRPC患者的中位生存期往往小于20个月,对于这部分患者的治疗方法十分有限。由于CRPC发生和发展机制不甚明了,近年来针对这方面的研究成为了人们关注的一个热点,其中涉及以雄激素受体(androgen receptor,AR)信号通路为主的多条分子信号通路[其它包括磷脂酰肌醇3-激酶/蛋白激酶B、丝裂原活化蛋白激酶、Hedgehog(Hh)、Wnt/β-钙黏蛋白以及信号转导和转录激活因子5等)之间的复杂调控作用及相互关联。研究这些分子信号通路在CRPC中的具体机制将为临床分子靶向治疗药物的研发提供新的靶点,对于解决目前CRPC治疗的瓶颈,控制患者的前列腺特异性抗原(prostate specii c antigen,PSA)水平和临床症状,改善生活质量,提高总生存率具有积极的意义。现就CRPC分子信号通路研究的最新进展作一综述。展开更多
文摘Aim: To investigate the androgen receptor (AR) isoform expressions in human prostatic cancer tissue and LNCaPcell line. Methods: With high resolution isoelectric focusing (IEF) method we demonstrated the different expres-sions of AR isoforms in human prostatic cancer tissues and LNCaP cell line. Results; Data were obtained from threeprostatic cancer specimens and the LNCaP cell line. Three types of AR isoforms were detected with pI values at 6.5,6.0, and 5.3. For the 3 prostatic cancer specimens, 1 sample showed all the three types of AR isoforms, the secondspecimen expressed at 6.5 and 6.0, and the third failed to show any type of isoforms. The LNCaP cell line expressedall the three AR isoforms. Binding of ~3H-dihydrotestosterone (~3H-DHT) to these three isoforms was inhibited by the ad-dition of 100-fold excess of DHT or testosterone, while not by progesterone, oestradiol and diethylstilboestrol. Conclu-sion : The expression of AR isoforms is different in different prostate cancer tissues, which may be related to the dif-ference in the effect of anti-androgen therapy in different patients. (Asian J Androl 2001 Sep; 3: 223 - 225)
文摘Aim: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatictissues. Methods: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from pa-tients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPHspecimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4℃, the tissues were ex-amined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. Results:From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In humanBPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 iso-fora at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 iso-forms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at differ-ent combinations. Binding of ~3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-foldexcess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. Conclusion: AR isoforms aredifferent in different patients. Although their genesis is not clear, the therapeutic implication of the present observationappears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.(Asian J Androl 2000 Dec; 2: 307-310)
文摘目的观察补骨脂素对体外培养的前列腺癌LNCa P-AD细胞增殖的抑制作用,并探讨补骨脂素抑制前列腺癌的作用机制。方法体外培养前列腺癌LNCa P-AD细胞,加入不同浓度的补骨脂素,CCK-8法检测细胞增殖抑制率、实时荧光定量PCR检测细胞AR m RNA的表达、Western Blot检测细胞PCNA和AR蛋白表达。采用单因素方差分析进行组间均数比较。结果与对照组相比,30、50、100μg/ml补骨脂素组LNCa P-AD细胞存活率均明显下降(P<0.05),补骨脂素对LNCa P-AD细胞增殖的抑制作用呈浓度-时间依赖性。实时荧光定量PCR检测结果显示,与对照组(1.00±0.00)相比,30μg/ml组AR m RNA表达上调(1.63±0.04,t=17.72,P<0.01),50μg/ml组AR m RNA表达无明显变化(0.98±0.04,t=0.66,P=0.53)、而100μg/ml组的AR m RNA表达则明显降低(0.46±0.07,t=15.18,P<0.01)。Western blot法检测结果显示,30μg/ml、50μg/ml、100μg/ml的补骨脂素干预48 h后,LNCa P-AD细胞PCNA蛋白表达均显著降低(11.88±0.21 vs 10.61±0.17 vs 6.62±0.13 vs 2.71±0.43,F=68.53,P<0.01)。100μg/ml的补骨脂素可明显降低LNCa P-AD细胞AR蛋白的表达水平(0.43±0.06 vs 0.87±0.04,t=6.04,P<0.01)。结论补骨脂素能在体外抑制前列腺癌LNCa P-AD细胞增殖,且呈剂量-时间依赖性,其机制可能与其下调LNCa P-AD细胞PCNA表达和影响AR表达有关。
文摘前列腺癌的发病率逐年上升,大多数中晚期前列腺癌患者最终都会进展至去势抵抗性前列腺癌(castrationresistant prostate cancer,CRPC)。CRPC患者的中位生存期往往小于20个月,对于这部分患者的治疗方法十分有限。由于CRPC发生和发展机制不甚明了,近年来针对这方面的研究成为了人们关注的一个热点,其中涉及以雄激素受体(androgen receptor,AR)信号通路为主的多条分子信号通路[其它包括磷脂酰肌醇3-激酶/蛋白激酶B、丝裂原活化蛋白激酶、Hedgehog(Hh)、Wnt/β-钙黏蛋白以及信号转导和转录激活因子5等)之间的复杂调控作用及相互关联。研究这些分子信号通路在CRPC中的具体机制将为临床分子靶向治疗药物的研发提供新的靶点,对于解决目前CRPC治疗的瓶颈,控制患者的前列腺特异性抗原(prostate specii c antigen,PSA)水平和临床症状,改善生活质量,提高总生存率具有积极的意义。现就CRPC分子信号通路研究的最新进展作一综述。
