Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects...Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.展开更多
BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained...BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.展开更多
九次跨膜超家族蛋白成员1(transmembrane 9 superfamily protein member 1,TM9SF1)在进化过程中高度保守,在人体组织和多种细胞系广泛表达。目前,关于该蛋白质的功能研究十分有限和初步。本研究采用慢病毒介导的TM9SF1表达系统,研究了重...九次跨膜超家族蛋白成员1(transmembrane 9 superfamily protein member 1,TM9SF1)在进化过程中高度保守,在人体组织和多种细胞系广泛表达。目前,关于该蛋白质的功能研究十分有限和初步。本研究采用慢病毒介导的TM9SF1表达系统,研究了重组TM9SF1蛋白的生化特点及其对细胞生长的调控作用。慢病毒感染的293T全细胞裂解液的蛋白质免疫印迹结果揭示,TM9SF1蛋白具有表观分子质量约为70 k D的单体及寡聚体两种主要形式;在室温及加热37℃时蛋白质相对稳定,随变性温度升高(56℃以上)逐渐失去其稳定性。CCK8法显示,与慢病毒空载体感染的293T细胞比较,TM9SF1慢病毒表达载体感染的293T细胞在感染2 d后增殖明显减缓(P<0.001)。Western印迹结果证明,过表达TM9SF1引起LC3Ⅱ表达明显上调,LC3Ⅱ/LC3Ⅰ比例升高,说明TM9SF1可引起293T细胞发生自噬。荧光实时定量PCR结果显示,过表达TM9SF1的293T细胞内质网应激标志分子CHOP、GADD34和XBP1(S)表达水平是对照细胞的3~4倍,提示发生了内质网应激反应。以上结果提示,TM9SF1具有抑制293T细胞生长的功能,该功能可能与其引起的内质网应激和自噬有关。这一结论将进一步加深对TM9SF1在细胞生长调控中的功能的认识。展开更多
探究9次跨膜超家族蛋白2(transmembrane 9 superfamily protein member 2,TM9SF2)对于三阴性乳腺癌MDA-MB-231细胞增殖和转移的影响及其分子机制。采用Western blot实验检测三阴性乳腺癌细胞株MDA-MB-231和非致瘤的乳腺上皮细胞株MCF-10...探究9次跨膜超家族蛋白2(transmembrane 9 superfamily protein member 2,TM9SF2)对于三阴性乳腺癌MDA-MB-231细胞增殖和转移的影响及其分子机制。采用Western blot实验检测三阴性乳腺癌细胞株MDA-MB-231和非致瘤的乳腺上皮细胞株MCF-10A中TM9SF2蛋白表达的情况;对高表达TM9SF2的三阴性细胞株MDA-MB-231进行基因沉默;采用MTS法检测细胞增殖活性,采用Transwell实验和划痕实验检测细胞的转移能力;采用Western blot实验检测细胞内增殖相关蛋白(PI3K、AKT、SRC和ERK)和转移相关蛋白(Snail、Slug和N-cadherin)的表达情况。Western blot实验证明,MDA-MB-231中TM9SF2蛋白的表达量高于MCF-10A细胞。与对照组相比,siRNA-TM9SF2转染组TM9SF2蛋白表达下调,细胞增殖活性降低,细胞转移能力减弱,PI3K、Snail、Slug和N-cadherin表达水平均降低,AKT蛋白磷酸化激活降低。研究结果表明,TM9SF2基因能促进三阴型乳腺癌MDA-MB-231细胞的增殖和转移。展开更多
OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spheri...OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.展开更多
文摘Zhuo et al looked into the part of transmembrane 9 superfamily member 1(TM9SF1)in bladder cancer(BC),and evaluated if it can be used as a therapeutic target.They created a permanent BC cell line and tested the effects of TM9SF1 overexpression and suppression on BC cell growth,movement,invasion,and cell cycle advancement.Their results show that TM9SF1 can boost the growth,movement,and invasion of BC cells and their access into the G2/M stage of the cell cycle.This research gives a novel direction and concept for targeted therapy of BC.
基金Supported by National Natural Science Foundation of China,No.82260785.
文摘BACKGROUND Bladder cancer(BC)is the most common urological tumor.It has a high recur-rence rate,displays tutor heterogeneity,and resists chemotherapy.Furthermore,the long-term survival rate of BC patients has remained unchanged for decades,which seriously affects the quality of patient survival.To improve the survival rate and prognosis of BC patients,it is necessary to explore the molecular mechanisms of BC development and progression and identify targets for treatment and intervention.Transmembrane 9 superfamily member 1(TM9SF1),also known as MP70 and HMP70,is a member of a family of nine transmembrane superfamily proteins,which was first identified in 1997.TM9SF1 can be expressed in BC,but its biological function and mechanism in BC are not clear.AIM To investigate the biological function and mechanism of TM9SF1 in BC.Overexpression of TM9SF1 increased the in vitro proliferation,migration,and invasion of BC cells by promoting the entry of BC cells into the G2/M phase.Silencing of TM9SF1 inhibited in vitro proliferation,migration,and invasion of BC cells and blocked BC cells in the G1 phase.CONCLUSION TM9SF1 may be an oncogene in BC.
文摘九次跨膜超家族蛋白成员1(transmembrane 9 superfamily protein member 1,TM9SF1)在进化过程中高度保守,在人体组织和多种细胞系广泛表达。目前,关于该蛋白质的功能研究十分有限和初步。本研究采用慢病毒介导的TM9SF1表达系统,研究了重组TM9SF1蛋白的生化特点及其对细胞生长的调控作用。慢病毒感染的293T全细胞裂解液的蛋白质免疫印迹结果揭示,TM9SF1蛋白具有表观分子质量约为70 k D的单体及寡聚体两种主要形式;在室温及加热37℃时蛋白质相对稳定,随变性温度升高(56℃以上)逐渐失去其稳定性。CCK8法显示,与慢病毒空载体感染的293T细胞比较,TM9SF1慢病毒表达载体感染的293T细胞在感染2 d后增殖明显减缓(P<0.001)。Western印迹结果证明,过表达TM9SF1引起LC3Ⅱ表达明显上调,LC3Ⅱ/LC3Ⅰ比例升高,说明TM9SF1可引起293T细胞发生自噬。荧光实时定量PCR结果显示,过表达TM9SF1的293T细胞内质网应激标志分子CHOP、GADD34和XBP1(S)表达水平是对照细胞的3~4倍,提示发生了内质网应激反应。以上结果提示,TM9SF1具有抑制293T细胞生长的功能,该功能可能与其引起的内质网应激和自噬有关。这一结论将进一步加深对TM9SF1在细胞生长调控中的功能的认识。
文摘探究9次跨膜超家族蛋白2(transmembrane 9 superfamily protein member 2,TM9SF2)对于三阴性乳腺癌MDA-MB-231细胞增殖和转移的影响及其分子机制。采用Western blot实验检测三阴性乳腺癌细胞株MDA-MB-231和非致瘤的乳腺上皮细胞株MCF-10A中TM9SF2蛋白表达的情况;对高表达TM9SF2的三阴性细胞株MDA-MB-231进行基因沉默;采用MTS法检测细胞增殖活性,采用Transwell实验和划痕实验检测细胞的转移能力;采用Western blot实验检测细胞内增殖相关蛋白(PI3K、AKT、SRC和ERK)和转移相关蛋白(Snail、Slug和N-cadherin)的表达情况。Western blot实验证明,MDA-MB-231中TM9SF2蛋白的表达量高于MCF-10A细胞。与对照组相比,siRNA-TM9SF2转染组TM9SF2蛋白表达下调,细胞增殖活性降低,细胞转移能力减弱,PI3K、Snail、Slug和N-cadherin表达水平均降低,AKT蛋白磷酸化激活降低。研究结果表明,TM9SF2基因能促进三阴型乳腺癌MDA-MB-231细胞的增殖和转移。
基金supported by the Grantin-Aid for scientific research(B)No.18300164"Screening of carcinoma cell surface markers and its application in molecular targeting with bionanocapsules"Japan Society for the Promotion of Science(JSPS).
文摘OBJECTIVE We aimed identification of cell surface molecules, which might serve as diagnostic biomarkers or useful targets for therapies, in breast cancer. METHODS We developed unique DNA microarray coupled with spherical self-organizing map （sSOM） analysis to characterize cells and tissues by the cell surface markers. In the microarray 1,797 probes for human genes coding membrane bound proteins were spotted. With this microarray the gene expression profiles of eight breast carcinoma cell lines were compared to identify the genes that were commonly expressed in breast carcinomas but not in normal cells. RESULTS The gene expression profiles of sSOM from the eight breast carcinoma cell lines were successfully distinguished from that of normal breast tissue derived cells suggesting the presence of genes of interest, sSOMon the data extensively filtered revealed several candidate genes, of which expression was significant in carcinoma cells but low in normal cells. Finally, TM9SF2 was nominated through validations of PCR procedures together with CD24 and ErbB3, which are known breast carcinoma markers. TMgSF2 expression was further confirmed by immunological staining. Interestingly, TMgSF2 was found to be expressed in all the cell lines evaluated while CD24 and ErbB3 were not in all of the carcinoma cells, supporting their relationship in sSOM. Although physiological significance of TMgSF2 is unknown yet, siRNA treatment significantly inhibited the growth of MDA- MB-231 cells. CONCLUSION We propose TM9SF2 as a novel and useful diagnostic marker as well as a potential molecular target specific to breast carcinoma cells covering wide range of breast cancer.
