During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that...During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 （TRPM8）, TRP vanilloid 6 （TRPV6）,TRP canonical （TRPC6） and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.展开更多
Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insec...Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insect survival and reproduction.In this study,we identifed and cloned two variants of the TRPA subfamily gene in Myzus persicae,MperTRPA1(A)and MperTRPA1(B),and analyzed their tissue expression by real-time quantitative PCR.Subsequently,these two variants of MperTRPA1 were expressed in the Xenopus oocyte system,and their functions were investigated using the two-electrode voltage clamp technique.The role of the MperTRPA1 gene in temperature adaptation of M.persicae was further determined by RNA interference and a behavioral choice assay to evaluate responses to temperature gradients.The results showed that the MperTRPA1 gene is widely expressed in tissues of M.persicae,with MperTRPA1(A)highly expressed in the mouthparts and MperTRPA1(B)mainly expressed in the antennae.The functional characterization results showed that both variants of MperTRPA1 could be activated and were not desensitized when the temperature increased from 20 to 45℃.The current value and thermal sensitivity(coeffcient Q_(10)value)of MperTRPA1(B)were signifcantly higher than those of MperTRPA1(A).When the MperTRPA1 gene was knocked down,the behavioral preference of M.persicae for the optimal temperature was reduced and tended to be at a higher temperature,showing a shift in the temperature adaptation range compared to both the wild type and ds GFP-treated M.persicae.In summary,our results elucidated the molecular mechanism of adaptive temperature perception in M.persicae mediated by the thermal sensor MperTRPA1.展开更多
背景与目的:前列腺癌与乳腺癌作为高发恶性肿瘤,其发生、发展与抑癌基因10号染色体上缺失的磷酸酶与张力蛋白同源物基因(phosphatase and tensin homolog deleted on chremosome ten,Pten)及转化相关蛋白53基因(transformation related ...背景与目的:前列腺癌与乳腺癌作为高发恶性肿瘤,其发生、发展与抑癌基因10号染色体上缺失的磷酸酶与张力蛋白同源物基因(phosphatase and tensin homolog deleted on chremosome ten,Pten)及转化相关蛋白53基因(transformation related protein 53 gene,Trp53)的功能缺失密切相关,二者同时缺失可加速肿瘤恶性进展并诱导治疗抵抗。基于Cre-loxP系统的基因编辑小鼠自发性肿瘤模型是研究癌症机制的关键工具。研究表明,前列腺特异性启动子前泌蛋白(probasin,Pbsn)的基因驱动的iCre重组酶基因(Pbsn-iCre)可诱导雄性小鼠自发性前列腺癌,但其在雌性乳腺癌中的作用及跨性别表达特征尚未阐明。本研究构建Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)转基因小鼠模型,旨在探究其在前列腺癌与乳腺癌中的自发性肿瘤表型,并验证Pbsn在乳腺组织中的表达特征。方法:利用Cre-loxP系统,通过杂交及连续回交筛选获得基因型稳定的Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)子代小鼠(伦理审查批号:FUSCC-IACUC-2025115)。通过聚合酶链式反应及琼脂糖凝胶电泳验证Pten、Trp53及Pbsn-iCre基因型。通过H-E染色评估肿瘤组织病理学特征。免疫组织化学分析前列腺及乳腺肿瘤组织中Pten、p53蛋白表达水平,并检测Pbsn在乳腺、前列腺、卵巢、心脏、肝脏及肾脏中的分布。结果:Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)雄鼠与雌鼠分别自发前列腺癌或乳腺癌。前列腺癌病理学特征表现为肿瘤呈侵袭性腺泡腺癌结构,伴腺体结构紊乱及基膜破坏;乳腺癌病理学特征表现为浸润性导管癌,伴导管上皮异型增生及间质淋巴细胞浸润。免疫组织化学检测证实前列腺及乳腺的肿瘤组织中Pten与p53蛋白完全失表达,验证了前列腺和乳腺特异性基因敲除效应。免疫组织化学检测也证实了Pbsn蛋白特异性表达于前列腺腺泡上皮、卵泡及乳腺导管上皮细胞,而心脏、肝脏及肾脏中未见表达。结论:Pbsn-iCre在雌性乳腺中存在功能性表达,Pbsn-iCre所诱导的Pten/Trp53同时缺失可驱动雄鼠自发形成前列腺癌、雌鼠自发形成乳腺癌。展开更多
文摘During the last decade, transient receptor potential （TRP） channels emerge as key proteins in central mechanisms of the carcinogenesis such as cell proliferation, apoptosis and migration. Initial studies showed that expression profile of some TRP channels, notably TRP melastatin 8 （TRPM8）, TRP vanilloid 6 （TRPV6）,TRP canonical （TRPC6） and TRPV2, is changing during the development and the progression of prostate cancer towards the hormone-refractory stages. The link between the change in expression levels and the functional role of these channels in prostate cancer is step by step being elucidated. These recent advances are here described and discussed.
基金funded by the National Natural Science Foundation of China(32472553 and 31872039)the Major Special Projects for Green Pest Control,China(110202201017(LS-01))+1 种基金the Shenzhen Science and Technology Program,China(KQTD20180411143628272)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciences。
文摘Transient receptor potential(TRP)channels are a class of ion channel proteins that are closely related to thermosensation in insects.They are involved in detecting the ambient temperature and play vital roles in insect survival and reproduction.In this study,we identifed and cloned two variants of the TRPA subfamily gene in Myzus persicae,MperTRPA1(A)and MperTRPA1(B),and analyzed their tissue expression by real-time quantitative PCR.Subsequently,these two variants of MperTRPA1 were expressed in the Xenopus oocyte system,and their functions were investigated using the two-electrode voltage clamp technique.The role of the MperTRPA1 gene in temperature adaptation of M.persicae was further determined by RNA interference and a behavioral choice assay to evaluate responses to temperature gradients.The results showed that the MperTRPA1 gene is widely expressed in tissues of M.persicae,with MperTRPA1(A)highly expressed in the mouthparts and MperTRPA1(B)mainly expressed in the antennae.The functional characterization results showed that both variants of MperTRPA1 could be activated and were not desensitized when the temperature increased from 20 to 45℃.The current value and thermal sensitivity(coeffcient Q_(10)value)of MperTRPA1(B)were signifcantly higher than those of MperTRPA1(A).When the MperTRPA1 gene was knocked down,the behavioral preference of M.persicae for the optimal temperature was reduced and tended to be at a higher temperature,showing a shift in the temperature adaptation range compared to both the wild type and ds GFP-treated M.persicae.In summary,our results elucidated the molecular mechanism of adaptive temperature perception in M.persicae mediated by the thermal sensor MperTRPA1.
文摘背景与目的:前列腺癌与乳腺癌作为高发恶性肿瘤,其发生、发展与抑癌基因10号染色体上缺失的磷酸酶与张力蛋白同源物基因(phosphatase and tensin homolog deleted on chremosome ten,Pten)及转化相关蛋白53基因(transformation related protein 53 gene,Trp53)的功能缺失密切相关,二者同时缺失可加速肿瘤恶性进展并诱导治疗抵抗。基于Cre-loxP系统的基因编辑小鼠自发性肿瘤模型是研究癌症机制的关键工具。研究表明,前列腺特异性启动子前泌蛋白(probasin,Pbsn)的基因驱动的iCre重组酶基因(Pbsn-iCre)可诱导雄性小鼠自发性前列腺癌,但其在雌性乳腺癌中的作用及跨性别表达特征尚未阐明。本研究构建Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)转基因小鼠模型,旨在探究其在前列腺癌与乳腺癌中的自发性肿瘤表型,并验证Pbsn在乳腺组织中的表达特征。方法:利用Cre-loxP系统,通过杂交及连续回交筛选获得基因型稳定的Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)子代小鼠(伦理审查批号:FUSCC-IACUC-2025115)。通过聚合酶链式反应及琼脂糖凝胶电泳验证Pten、Trp53及Pbsn-iCre基因型。通过H-E染色评估肿瘤组织病理学特征。免疫组织化学分析前列腺及乳腺肿瘤组织中Pten、p53蛋白表达水平,并检测Pbsn在乳腺、前列腺、卵巢、心脏、肝脏及肾脏中的分布。结果:Pten^(fl/fl);Trp53^(fl/fl);Pbsn-iCre^(+)雄鼠与雌鼠分别自发前列腺癌或乳腺癌。前列腺癌病理学特征表现为肿瘤呈侵袭性腺泡腺癌结构,伴腺体结构紊乱及基膜破坏;乳腺癌病理学特征表现为浸润性导管癌,伴导管上皮异型增生及间质淋巴细胞浸润。免疫组织化学检测证实前列腺及乳腺的肿瘤组织中Pten与p53蛋白完全失表达,验证了前列腺和乳腺特异性基因敲除效应。免疫组织化学检测也证实了Pbsn蛋白特异性表达于前列腺腺泡上皮、卵泡及乳腺导管上皮细胞,而心脏、肝脏及肾脏中未见表达。结论:Pbsn-iCre在雌性乳腺中存在功能性表达,Pbsn-iCre所诱导的Pten/Trp53同时缺失可驱动雄鼠自发形成前列腺癌、雌鼠自发形成乳腺癌。
