Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m ce...Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.展开更多
Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting ...Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.展开更多
Mitogen-activated protein kinase-8-interacting protein 2(MAPK8IP2)is a scaffold protein that modulates MAPK signal cascades.Although MAPK pathways were heavily implicated in prostate cancer progression,the regulation ...Mitogen-activated protein kinase-8-interacting protein 2(MAPK8IP2)is a scaffold protein that modulates MAPK signal cascades.Although MAPK pathways were heavily implicated in prostate cancer progression,the regulation of MAPK8IP2 expression in prostate cancer is not yet reported.We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes.MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas(TCGA)RNA-sequence project and complementary DNA(cDNA)microarrays.Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval.MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach.The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells.In primary prostate cancer tissues,MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues.Increased MAPK8IP2 expression was strongly correlated with late tumor stages,lymph node invasion,residual tumors after surgery,higher Gleason scores,and preoperational serum prostate-specific antigen(PSA)levels.MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals.In castration-resistant prostate cancers,MAPK8IP2 expression strongly correlated with androgen receptor(AR)signaling activity.In cell culture-based experiments,MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells.However,MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells.These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer.The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.展开更多
目的:探讨视网膜母细胞瘤易感基因(Rb)和微染色体维持蛋白2(MCM2)在前列腺癌发病机制中的作用及其临床意义。方法:应用免疫组化EliVisionTM plus二步法,检测49例前列腺癌(PCa)组织,20例良性前列腺增生(BPH)及10例正常前列腺组织(NP)中pR...目的:探讨视网膜母细胞瘤易感基因(Rb)和微染色体维持蛋白2(MCM2)在前列腺癌发病机制中的作用及其临床意义。方法:应用免疫组化EliVisionTM plus二步法,检测49例前列腺癌(PCa)组织,20例良性前列腺增生(BPH)及10例正常前列腺组织(NP)中pRb蛋白与M CM 2的表达。结果:pRb在PCa,BPH与NP组织中的阳性表达率分别为44.90%,80%,90%,PCa中pRb的水平明显低于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级(P<0.05)和临床分期(P<0.05)呈负相关。M CM 2在PCa,BPH与NP组织中的阳性表达率分别为67.35%,25%和10%,PCa中M CM 2的水平明显高于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级(P<0.05)和临床分期(P<0.05)呈正相关。M CM 2表达与pRb表达呈负相关(rs=-0.596,P<0.01)。结论:Rb基因参与了前列腺癌的发生、发展过程,检测Rb基因和M CM 2有助于判定前列腺癌恶性程度及预后。展开更多
文摘Aim: To investigate the effect of abrogating heat shock protein (HSP) 70 expression by antisense HSP70 oligonucleotides treatment on human androgen-independent prostate cancer cell line PC-3m growth. Methods: PC-3m cells were treated with 0-16 μmol/L antisense HSP70 oligomers for 0-100 hr. Cell growth inhibition was analyzed using a trypan blue dye exclusion test. Apoptotic cells were detected and confirmed by flow cytometric analysis and DNA fragmentation analysis. The protein expression of HSP70 and bcl-2 affected by antisense HSP70 oligomers were determined using Western blot. Results: Antisense HSP70 oligomer induced apoptosis and then inhibited proliferation of PC-3m cells in a dose- and time-dependent manner. Ladder-like patterns of DNA fragments were observed in PC-3m cells treated with 10 μmol/L antisense HSP70 oligomer for 48 hr or 8 μmol/L for 72 hr on agarose gel electrophoresis. Antisense HSP70 oligomer pretreatment enhanced the subsequent induction of apoptosis by heat shock in PC-3m cells. In addition, undetectable HSP70 expression was observed at a concentration of 10 μmol/L antisense HSP70 oligomer treatment for 48 hr or 8 μmol/L for 72 hr in Western blot, which was paralleled by decreased expression levels of anti-apoptotic protein bcl-2. Conclusion: HSP70 antisense oligomer treatment abrogates the expression of HSP70, which may disrupt HSP70-bcl-2-interactions and further down-regulate bcl-2 expression, in turn inducing apoptosis and inhibiting cell growth in PC-3m cells.
文摘Defects within apoptotic pathways have been implicated in prostate cancer （PCa） tumorigenesis, metastatic progression and treatment resistance. A hallmark of cancers is the ability to derail apoptosis by inhibiting the apoptotic signal, reducing the expression of apoptotic proteins and/or amplifying survival signals through increased production of antiapoptotic molecule. This review describes associations between heat shock proteins （HSPs） and the human androgen receptor （AR）, the role of HSPs and other stress-induced proteins in PCa development and emerging strategies in targeting these protective proteins to treat PCa.
文摘Mitogen-activated protein kinase-8-interacting protein 2(MAPK8IP2)is a scaffold protein that modulates MAPK signal cascades.Although MAPK pathways were heavily implicated in prostate cancer progression,the regulation of MAPK8IP2 expression in prostate cancer is not yet reported.We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes.MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas(TCGA)RNA-sequence project and complementary DNA(cDNA)microarrays.Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval.MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach.The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells.In primary prostate cancer tissues,MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues.Increased MAPK8IP2 expression was strongly correlated with late tumor stages,lymph node invasion,residual tumors after surgery,higher Gleason scores,and preoperational serum prostate-specific antigen(PSA)levels.MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals.In castration-resistant prostate cancers,MAPK8IP2 expression strongly correlated with androgen receptor(AR)signaling activity.In cell culture-based experiments,MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells.However,MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells.These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer.The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.
文摘目的:探讨视网膜母细胞瘤易感基因(Rb)和微染色体维持蛋白2(MCM2)在前列腺癌发病机制中的作用及其临床意义。方法:应用免疫组化EliVisionTM plus二步法,检测49例前列腺癌(PCa)组织,20例良性前列腺增生(BPH)及10例正常前列腺组织(NP)中pRb蛋白与M CM 2的表达。结果:pRb在PCa,BPH与NP组织中的阳性表达率分别为44.90%,80%,90%,PCa中pRb的水平明显低于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级(P<0.05)和临床分期(P<0.05)呈负相关。M CM 2在PCa,BPH与NP组织中的阳性表达率分别为67.35%,25%和10%,PCa中M CM 2的水平明显高于BPH(P<0.05)及NP(P<0.05),且与PCa病理分级(P<0.05)和临床分期(P<0.05)呈正相关。M CM 2表达与pRb表达呈负相关(rs=-0.596,P<0.01)。结论:Rb基因参与了前列腺癌的发生、发展过程,检测Rb基因和M CM 2有助于判定前列腺癌恶性程度及预后。
