Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres e...Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer ceils express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the selfrenewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.展开更多
本文主要研究肾阳虚(kidney yang deficiency)小鼠血清睾酮及性腺雄激素受体基因的表达,旨在揭示淫羊藿苷(icariin)对肾阳虚症状的影响.雄性小鼠随机分为6组,除正常组注射生理盐水外,其余组注射氢化可的松15 d;再分别给大、中、小剂量...本文主要研究肾阳虚(kidney yang deficiency)小鼠血清睾酮及性腺雄激素受体基因的表达,旨在揭示淫羊藿苷(icariin)对肾阳虚症状的影响.雄性小鼠随机分为6组,除正常组注射生理盐水外,其余组注射氢化可的松15 d;再分别给大、中、小剂量组淫羊藿苷,阳性组甲基睾酮,正常组和模型对照组蒸馏水,灌胃15 d.放射免疫法测血清中睾酮含量;RT-PCR和免疫组织化学方法检测雄激素受体基因在性腺组织中mRNA和蛋白质的表达情况.对照组小鼠平均体重最轻,与正常组比较差异显著(P<0.05).对照组小鼠血清睾酮的含量显著低于正常组(P<0.05);大、中剂量给药组,阳性组睾酮与正常组相比差异不显著(P>0.05);性腺组织中,对照组雄激素受体和mRNA比正常组表达量低,差异显著(P<0.05);中、小剂量给药组,阳性组雄激素受体和mRNA与正常组相比差异不显著(P>0.05).结果表明,肾阳虚小鼠血清睾酮含量,性腺雄激素受体mRNA和蛋白质的表达与正常组相比均有所下降,淫羊藿苷能够抑制其下降,缓解肾阳虚症状.展开更多
Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have bee...Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have been directed to the interactions between cancer cells and the bone microenvironment,including osteoclasts,osteoblasts,and bone stromal cells.Here,we explained the mechanism of interactions between prostate cancer cells and metastasis-associated cells within the bone microenvironment and further discussed the recent advances in targeted therapy of prostate cancer bone metastasis.This review also summarized the effects of bone microenvironment on prostate cancer metastasis and the related mechanisms,and provides insights for future prostate cancer metastasis studies.展开更多
Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject ...Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.展开更多
Prostate cancer （PCa） is the second most common malignancy among men in the world. Castration-resistant prostate cancer （CRPC） is the lethal form of the disease, which develops upon resistance to first line androg...Prostate cancer （PCa） is the second most common malignancy among men in the world. Castration-resistant prostate cancer （CRPC） is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy （ADT）. Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor （AR） signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.展开更多
Aim： To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods： Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation ...Aim： To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods： Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor （AR）, prostate-specific antigen （PSA）, p53, p21, Bcl-2, Bax, caspase-3, -8, -9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. Results： In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax/Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. Conclusion： In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.展开更多
Background and Objective:Androgen receptor(AR) is involved in the pathogenesis of breast cancer,but its role is not clearly defined.This study was to explore the expression of AR and its relationship with clinicopatho...Background and Objective:Androgen receptor(AR) is involved in the pathogenesis of breast cancer,but its role is not clearly defined.This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer(negative estrogen receptor,negative progesterone receptor,and negative Her-2).Methods:Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative breast cancer.The relationships between AR expression and clinicopathologic data and prognosis were analyzed.Results:The positive rate of AR was significantly lower in triple negative breast cancer than in non-triple negative breast(27.7% vs.83.3%,χ2 = 83.963,P < 0.001).AR expression was correlated with menorrheal status(χ2 = 6.803,P = 0.009),tumor grade(χ2 = 5.173,P = 0.023),node status(χ2 = 7.787,P = 0.005),5-year disease-free survival(χ2 = 5.012,P = 0.025) and 5-year overall survival(χ2 = 5.552,P = 0.018) in triple negative breast cancer,but was not correlated with clinicopathologic parameters and survival in non-triple negative breast cancer.The 5-year overall survival rate was 78.8% in triple negative breast cancer and 83.3% in non-triple negative breast cancer.Conclusions:The expression of AR is related to biological behaviors of triple negative breast cancer,and plays a role in endocrinotherapy and prognostic prediction.展开更多
文摘Prostate cancer cells with stem cell characteristics were identified in human prostate cancer cell lines by their ability to form from single cells self-renewing prostaspheres in non-adherent cultures. Prostaspheres exhibited heterogeneous expression of proliferation, differentiation and stem cell-associated makers CD44, ABCG2 and CD133. Treatment with WNT inhibitors reduced both prostasphere size and self-renewal. In contrast, addition of Wnt3a caused increased prostasphere size and self-renewal, which was associated with a significant increase in nuclear β-catenin, keratin 18, CD133 and CD44 expression. As a high proportion of LNCaP and C4-2B cancer ceils express androgen receptor we determined the effect of the androgen receptor antagonist bicalutamide. Androgen receptor inhibition reduced prostasphere size and expression of PSA, but did not inhibit prostasphere formation. These effects are consistent with the androgen-independent self-renewal of cells with stem cell characteristics and the androgen-dependent proliferation of transit amplifying cells. As the canonical WNT signaling effector β-catenin can also associate with the androgen receptor, we propose a model for tumour propagation involving a balance between WNT and androgen receptor activity. That would affect the self-renewal of a cancer cell with stem cell characteristics and drive transit amplifying cell proliferation and differentiation. In conclusion, we provide evidence that WNT activity regulates the selfrenewal of prostate cancer cells with stem cell characteristics independently of androgen receptor activity. Inhibition of WNT signaling therefore has the potential to reduce the self-renewal of prostate cancer cells with stem cell characteristics and improve the therapeutic outcome.
基金Supported by National Natural Science Foundation of China (No. 10874108)~~
文摘本文主要研究肾阳虚(kidney yang deficiency)小鼠血清睾酮及性腺雄激素受体基因的表达,旨在揭示淫羊藿苷(icariin)对肾阳虚症状的影响.雄性小鼠随机分为6组,除正常组注射生理盐水外,其余组注射氢化可的松15 d;再分别给大、中、小剂量组淫羊藿苷,阳性组甲基睾酮,正常组和模型对照组蒸馏水,灌胃15 d.放射免疫法测血清中睾酮含量;RT-PCR和免疫组织化学方法检测雄激素受体基因在性腺组织中mRNA和蛋白质的表达情况.对照组小鼠平均体重最轻,与正常组比较差异显著(P<0.05).对照组小鼠血清睾酮的含量显著低于正常组(P<0.05);大、中剂量给药组,阳性组睾酮与正常组相比差异不显著(P>0.05);性腺组织中,对照组雄激素受体和mRNA比正常组表达量低,差异显著(P<0.05);中、小剂量给药组,阳性组雄激素受体和mRNA与正常组相比差异不显著(P>0.05).结果表明,肾阳虚小鼠血清睾酮含量,性腺雄激素受体mRNA和蛋白质的表达与正常组相比均有所下降,淫羊藿苷能够抑制其下降,缓解肾阳虚症状.
基金This work was supported the National Natural Science Foundation of China(Nos.81803097 and 81602727)the Natural Science Foundation of Shandong Province(No.ZR2017QH005).
文摘Bone metastasis is the leading cause of death in prostate cancer patients,for which there is currently no effective treatment.Since the bone microenvironment plays an important role in this process,attentions have been directed to the interactions between cancer cells and the bone microenvironment,including osteoclasts,osteoblasts,and bone stromal cells.Here,we explained the mechanism of interactions between prostate cancer cells and metastasis-associated cells within the bone microenvironment and further discussed the recent advances in targeted therapy of prostate cancer bone metastasis.This review also summarized the effects of bone microenvironment on prostate cancer metastasis and the related mechanisms,and provides insights for future prostate cancer metastasis studies.
文摘Androgen receptor （AR） gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat （CAG and GGN） length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
文摘Prostate cancer （PCa） is the second most common malignancy among men in the world. Castration-resistant prostate cancer （CRPC） is the lethal form of the disease, which develops upon resistance to first line androgen deprivation therapy （ADT）. Emerging evidence demonstrates a key role for the PI3K-AKT-mTOR signaling axis in the development and maintenance of CRPC. This pathway, which is deregulated in the majority of advanced PCas, serves as a critical nexus for the integration of growth signals with downstream cellular processes such as protein synthesis, proliferation, survival, metabolism and differentiation, thus providing mechanisms for cancer cells to overcome the stress associated with androgen deprivation. Furthermore, preclinical studies have elucidated a direct connection between the PI3K-AKT-mTOR and androgen receptor （AR） signaling axes, revealing a dynamic interplay between these pathways during the development of ADT resistance. Thus, there is a clear rationale for the continued clinical development of a number of novel inhibitors of the PI3K pathway, which offer the potential of blocking CRPC growth and survival. In this review, we will explore the relevance of the PI3K-AKT-mTOR pathway in PCa progression and castration resistance in order to inform the clinical development of specific pathway inhibitors in advanced PCa. In addition, we will highlight current deficiencies in our clinical knowledge, most notably the need for biomarkers that can accurately predict for response to PI3K pathway inhibitors.
基金This study was supported by the Natural Science Foundation of Shandong Province （No. Y2005C29） and the National Natural Science Foundation of China （No. 30470820 and No. 30670581）.
文摘Aim： To elucidate effects and mechanisms of emodin in prostate cancer cells. Methods： Viability of emodin-treated LNCaP cells and PC-3 cells was measured by MTT assay. Following emodin treatments, DNA fragmentation was assayed by agarose gel electrophoresis. Apoptosis rate and the expression of Fas and FasL were assayed by flow cytometric analysis. The mRNA expression levels of androgen receptor （AR）, prostate-specific antigen （PSA）, p53, p21, Bcl-2, Bax, caspase-3, -8, -9 and Fas were detected by RT-PCR, and the protein expression levels of AR, p53 and p21 were detected by Western blot analysis. Results： In contrast to PC-3, emodin caused a marked increase in apoptosis and a decrease in cell proliferation in LNCaP cells. The expression of AR and PSA was decreased and the expression of p53 and p21 was increased as the emodin concentrations were increased. In the same time, emodin induced apoptosis of LNCaP cells through the upregulation of caspase-3 and -9, as well as the increase of Bax/Bcl-2 ratio. However, it did not involve modulation of Fas or caspase-8 protein expression. Conclusion： In prostate cancer cell line, LNCaP, emodin inhibites the proliferation by AR and p53-p21 pathways, and induces apoptosis via the mitochondrial pathway.
文摘Background and Objective:Androgen receptor(AR) is involved in the pathogenesis of breast cancer,but its role is not clearly defined.This study was to explore the expression of AR and its relationship with clinicopathologic parameters in triple negative breast cancer(negative estrogen receptor,negative progesterone receptor,and negative Her-2).Methods:Immunohistochemical assays were performed to determine the expression of AR in 137 cases of triple negative breast cancer and 132 cases of non-triple negative breast cancer.The relationships between AR expression and clinicopathologic data and prognosis were analyzed.Results:The positive rate of AR was significantly lower in triple negative breast cancer than in non-triple negative breast(27.7% vs.83.3%,χ2 = 83.963,P < 0.001).AR expression was correlated with menorrheal status(χ2 = 6.803,P = 0.009),tumor grade(χ2 = 5.173,P = 0.023),node status(χ2 = 7.787,P = 0.005),5-year disease-free survival(χ2 = 5.012,P = 0.025) and 5-year overall survival(χ2 = 5.552,P = 0.018) in triple negative breast cancer,but was not correlated with clinicopathologic parameters and survival in non-triple negative breast cancer.The 5-year overall survival rate was 78.8% in triple negative breast cancer and 83.3% in non-triple negative breast cancer.Conclusions:The expression of AR is related to biological behaviors of triple negative breast cancer,and plays a role in endocrinotherapy and prognostic prediction.
