Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal canc...Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients. Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed. Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients’ clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion: The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.展开更多
DLC1 is a focal adhesion molecule that regulates cell polarity,proliferation,migration,and survival.DLC1 functions as a tumor suppressor and its expression is often down-regulated in.various malignant neoplasms of epi...DLC1 is a focal adhesion molecule that regulates cell polarity,proliferation,migration,and survival.DLC1 functions as a tumor suppressor and its expression is often down-regulated in.various malignant neoplasms of epithelial origin.Recent studies have suggested that lack of DLC1 in endothelial cells may contribute to the development of angiosarcoma,and that DLC1 mutations have been identified in patients with nephrotic syndrome,a disease mainly due to leaky glomerular filtration barriers.To demonstrate whether lack of endothelial DLC1 induces angiosarcoma and/or damages glomerular capillaries leading to nephrotic syndrome,we have extended our analyses on endothelial cell-specific DLC1 knockout mice with focuses on their liver and kidney function.Mice were monitored up to 24 months of age.However,no histological or clinical difference was found between DLC1 knockout and wild type mice,indicating that lack of endothelial DLC1 alone does not compromise kidney and liver function in mice.展开更多
目的探讨散发性乳腺癌(Sporadic breast cancer,SBC)、乳腺异型导管上皮增生(Breast atypital ductal hyperplasia,BADH)及乳腺腺病(Breast adenosis,BA)组织中肝癌缺失基因1(Deleted in liver cancer-1,DLC1)启动子甲基化状态及其蛋白...目的探讨散发性乳腺癌(Sporadic breast cancer,SBC)、乳腺异型导管上皮增生(Breast atypital ductal hyperplasia,BADH)及乳腺腺病(Breast adenosis,BA)组织中肝癌缺失基因1(Deleted in liver cancer-1,DLC1)启动子甲基化状态及其蛋白表达的关系,及DLCl基因异常的表遗传学作用与SBC发生的关系。方法采用甲基特异性聚合酶链反应(Methylation specific polrmerase chainreaction,MSP)研究42例SBC、14例BADH、20例BA组织及5例健康成人女性外周血淋巴细胞中DLC1基因启动子甲基化状态并用免疫组织化学(EnVision法)研究SBC、BADH和BA中DLCl蛋白表达情况。结果 5例健康成人女性外周血淋巴细胞均为DLC1基因启动子甲基化阴性;SBC、BADH和BA中DCL1基因启动子CpG岛甲基化率分别为38.1%、35.7%和0。SBC和BADH的DLC1基因启动子甲基化阳性率显著高于BA;SBC与BADH之间DLC1基因启动子甲基化阳性率差异无统计学意义。SBC中DLC1蛋白表达阴性26例,表达下调16例,BADH中DLC1蛋白阴性6例,表达下调8例;BA未见DLC1蛋白表达阴性或下调。16例发生DLC1甲基化的SBC,有14例蛋白表达阴性,2例表达下调。5例发生甲基化的BADH组织,3例蛋白表达阴性,2例表达下调。SBC、BADH的DLC1蛋白的阳性率显著低于BA;SBC的DLC1蛋白阳性率显著低于BADH。DLC1非甲基化组其蛋白表达的强度明显高于甲基化组,差异有统计学意义。结论 DLC1基因启动子CpG岛甲基化是SBC发生过程中的早期事件,是其蛋白表达下降乃至失活的重要原因,可能在乳腺癌变过程中起重要生物学作用。展开更多
在癌细胞中,识别基因及其功能的改变对肿瘤的预防与治疗极其重要。大量证据显示抑癌基因(Deleted in liver cancer 1,DLC1),在癌细胞发生及转移的过程作为抑癌基因,其编码的蛋白是一种Rho GTPase的激活剂,可为治疗肿瘤策略提供良好机会...在癌细胞中,识别基因及其功能的改变对肿瘤的预防与治疗极其重要。大量证据显示抑癌基因(Deleted in liver cancer 1,DLC1),在癌细胞发生及转移的过程作为抑癌基因,其编码的蛋白是一种Rho GTPase的激活剂,可为治疗肿瘤策略提供良好机会。现就DLC1抑制多种肿瘤发生与转移及其调控机制的相关研究进行综述。展开更多
背景与目的:有研究发现,肝癌缺失基因1(DLC1)在多种肿瘤中低表达或不表达,其通过调节黏着斑激酶(FAK)、促分裂原活化蛋白激酶(MAPK)等影响肿瘤细胞的凋亡。而对于DLC1在卵巢癌中的表达及作用等的研究甚少,本实验采用DLC1基因转染该基因...背景与目的:有研究发现,肝癌缺失基因1(DLC1)在多种肿瘤中低表达或不表达,其通过调节黏着斑激酶(FAK)、促分裂原活化蛋白激酶(MAPK)等影响肿瘤细胞的凋亡。而对于DLC1在卵巢癌中的表达及作用等的研究甚少,本实验采用DLC1基因转染该基因表达缺失的人卵巢癌多药耐药细胞系OVCAR-3,观察转染前后该细胞对顺铂耐药性及FAK、p38MAPK的变化。方法:将OVCAR-3细胞分为3组,空白组为未经处理的OVCAR-3细胞,阴性对照组转染空质粒pEGFP-C3,实验组转染重组质粒pEGFP-C3-DLC1。RT-PCR和Western blot检测各组细胞中DLC1基因和蛋白的表达,四甲基偶氮唑蓝(MTT)法测定各组细胞对顺铂的半数抑制浓度(IC50),Western blot观察FAK、p38蛋白及其磷酸化水平的变化,流式细胞仪测定顺铂处理前后各组细胞凋亡率及周期分布改变。结果:DLC1基因和蛋白在实验组表达而空白对照组和阴性对照组均未见表达,实验组细胞与其他两组细胞相比,对顺铂的IC50较低(4.02 vs 4.99/4.90μmol/L,P<0.01),p-p38蛋白表达上升而p-FAK蛋白表达下降(3.02 vs 1.52/1.61,3.13 vs 9.03/8.99,P<0.01),顺铂处理前后实验组与其他两组细胞相比凋亡率增加(8.97%vs 1.81%/1.95%,30.68%vs 18.03%/20.33%,P<0.01),G1期细胞比例增加(65.80%vs 60.82%/59.80%,66.48%vs 55.42%/53.94%,P<0.05)。结论:转染DLC1基因可使OVCAR-3G1期细胞比例及凋亡率升高,对顺铂敏感性增加,该作用可能依赖于细胞内外源性DLC1基因的表达、p-FAK表达降低和p-p38表达增强。展开更多
目的：探讨乳腺癌中肝癌缺失基因1（deleted in liver Cancer-1，DLC1）和DLC1-mRNA的表达及其临床意义。方法：应用原位杂交技术和免疫组织化学EnVision二步法，检测52例乳腺浸润性导管癌和42例非癌乳腺组织（包括癌旁乳腺组织20例和...目的：探讨乳腺癌中肝癌缺失基因1（deleted in liver Cancer-1，DLC1）和DLC1-mRNA的表达及其临床意义。方法：应用原位杂交技术和免疫组织化学EnVision二步法，检测52例乳腺浸润性导管癌和42例非癌乳腺组织（包括癌旁乳腺组织20例和乳腺纤维腺瘤22例）中DLC1和DLC1-mRNA的表达，分析乳腺癌中DLC1和DLC1-mRNA的表达与患者年龄、肿瘤最大直径、组织学分级、腋窝淋巴结转移和TNM分期等临床病理参数的相关性。结果：DLC1和DLC1-mRNA在乳腺癌和非癌乳腺组织中的阳性表达率分别为（57．7％，50．0％）和（92．9％，90．5％），DLC1和DLC1-mRNA在乳腺癌中的表达率显著低于非癌乳腺组织（χ^2=14．717，P=0．000；χ^2=17．518，P=0．000），差异均有显著统计学意义（P〈0．001）。乳腺癌中DLCI和DLC1-mRNA的表达与组织学分级（L=-0．811，P=0．000；rs=-0．422，P〈0．05）、腋淋巴结转移（rs=0．410，P〈0．01；rs=-0．445，P〈0．01）和TNM分期（rs=-0．319，P〈0．05；rs=-0．405，P〈0．05）均呈负相关；DLCI—mRNA的表达与肿瘤最大直径（rs=-0．347，P〈0．05）亦呈负相关。DLC1与肿瘤最大直径（rs=0．073）和DLC1、DLC1-mRNA的表达与患者年龄（rs=0．077；rs=0．008）的相关性均无统计学意义（P〉0．05）。结论：DLC1蛋白和DLC1-mRNA在乳腺癌中呈低表达或失表达，在乳腺癌的恶性演进中扮演着重要角色。检测乳腺癌中DLC1和DLC1-mRNA的表达，结合相关临床病理参数，可作为判断乳腺癌生物学行为和预后的一个参考指标。展开更多
文摘Objective: Deleted in liver cancer 1 (DLC1) is a new candidate tumor suppressor gene, whose down-regulation or even silence will result from promoter hypermethylation in various human cancers including colorectal cancer (CRC). The aim of this study is to evaluate the diagnostic role of DLC1 gene methylation in the serum DNA from CRC patients. Methods: This study enrolled 85 CRC patients and 45 patients with benign colorectal diseases. Methylation-specific polymerase chain reaction (MSP) was used to determine the promoter methylation status of DLC1 gene in serum DNA. The combination of DLC1 methylation and conventional tumor markers was further analyzed. Results: Hypermethylation of DLC1 was detected in 42.4% (36/85) of CRC serums, while seldom in the benign controls (8.9%, 4/45) (P<0.001). The aberrant DLC1 methylation in serum DNA was not associated with patients’ clinicopathological features and elevated CEA/CA19-9 levels. Furthermore, the combinational analysis of CEA, CA19-9 and DLC1 methylation showed a higher sensitivity and no reduced diagnostic specificity than CEA and CA19-9 combination for CRC diagnosis. Conclusion: The serum DLC1 methylation may be a promising biomarker for the early detection of CRC, which will further increase the diagnostic efficiency in combination with CEA and CA19-9.
文摘DLC1 is a focal adhesion molecule that regulates cell polarity,proliferation,migration,and survival.DLC1 functions as a tumor suppressor and its expression is often down-regulated in.various malignant neoplasms of epithelial origin.Recent studies have suggested that lack of DLC1 in endothelial cells may contribute to the development of angiosarcoma,and that DLC1 mutations have been identified in patients with nephrotic syndrome,a disease mainly due to leaky glomerular filtration barriers.To demonstrate whether lack of endothelial DLC1 induces angiosarcoma and/or damages glomerular capillaries leading to nephrotic syndrome,we have extended our analyses on endothelial cell-specific DLC1 knockout mice with focuses on their liver and kidney function.Mice were monitored up to 24 months of age.However,no histological or clinical difference was found between DLC1 knockout and wild type mice,indicating that lack of endothelial DLC1 alone does not compromise kidney and liver function in mice.
文摘目的探讨散发性乳腺癌(Sporadic breast cancer,SBC)、乳腺异型导管上皮增生(Breast atypital ductal hyperplasia,BADH)及乳腺腺病(Breast adenosis,BA)组织中肝癌缺失基因1(Deleted in liver cancer-1,DLC1)启动子甲基化状态及其蛋白表达的关系,及DLCl基因异常的表遗传学作用与SBC发生的关系。方法采用甲基特异性聚合酶链反应(Methylation specific polrmerase chainreaction,MSP)研究42例SBC、14例BADH、20例BA组织及5例健康成人女性外周血淋巴细胞中DLC1基因启动子甲基化状态并用免疫组织化学(EnVision法)研究SBC、BADH和BA中DLCl蛋白表达情况。结果 5例健康成人女性外周血淋巴细胞均为DLC1基因启动子甲基化阴性;SBC、BADH和BA中DCL1基因启动子CpG岛甲基化率分别为38.1%、35.7%和0。SBC和BADH的DLC1基因启动子甲基化阳性率显著高于BA;SBC与BADH之间DLC1基因启动子甲基化阳性率差异无统计学意义。SBC中DLC1蛋白表达阴性26例,表达下调16例,BADH中DLC1蛋白阴性6例,表达下调8例;BA未见DLC1蛋白表达阴性或下调。16例发生DLC1甲基化的SBC,有14例蛋白表达阴性,2例表达下调。5例发生甲基化的BADH组织,3例蛋白表达阴性,2例表达下调。SBC、BADH的DLC1蛋白的阳性率显著低于BA;SBC的DLC1蛋白阳性率显著低于BADH。DLC1非甲基化组其蛋白表达的强度明显高于甲基化组,差异有统计学意义。结论 DLC1基因启动子CpG岛甲基化是SBC发生过程中的早期事件,是其蛋白表达下降乃至失活的重要原因,可能在乳腺癌变过程中起重要生物学作用。
文摘在癌细胞中,识别基因及其功能的改变对肿瘤的预防与治疗极其重要。大量证据显示抑癌基因(Deleted in liver cancer 1,DLC1),在癌细胞发生及转移的过程作为抑癌基因,其编码的蛋白是一种Rho GTPase的激活剂,可为治疗肿瘤策略提供良好机会。现就DLC1抑制多种肿瘤发生与转移及其调控机制的相关研究进行综述。
文摘背景与目的:有研究发现,肝癌缺失基因1(DLC1)在多种肿瘤中低表达或不表达,其通过调节黏着斑激酶(FAK)、促分裂原活化蛋白激酶(MAPK)等影响肿瘤细胞的凋亡。而对于DLC1在卵巢癌中的表达及作用等的研究甚少,本实验采用DLC1基因转染该基因表达缺失的人卵巢癌多药耐药细胞系OVCAR-3,观察转染前后该细胞对顺铂耐药性及FAK、p38MAPK的变化。方法:将OVCAR-3细胞分为3组,空白组为未经处理的OVCAR-3细胞,阴性对照组转染空质粒pEGFP-C3,实验组转染重组质粒pEGFP-C3-DLC1。RT-PCR和Western blot检测各组细胞中DLC1基因和蛋白的表达,四甲基偶氮唑蓝(MTT)法测定各组细胞对顺铂的半数抑制浓度(IC50),Western blot观察FAK、p38蛋白及其磷酸化水平的变化,流式细胞仪测定顺铂处理前后各组细胞凋亡率及周期分布改变。结果:DLC1基因和蛋白在实验组表达而空白对照组和阴性对照组均未见表达,实验组细胞与其他两组细胞相比,对顺铂的IC50较低(4.02 vs 4.99/4.90μmol/L,P<0.01),p-p38蛋白表达上升而p-FAK蛋白表达下降(3.02 vs 1.52/1.61,3.13 vs 9.03/8.99,P<0.01),顺铂处理前后实验组与其他两组细胞相比凋亡率增加(8.97%vs 1.81%/1.95%,30.68%vs 18.03%/20.33%,P<0.01),G1期细胞比例增加(65.80%vs 60.82%/59.80%,66.48%vs 55.42%/53.94%,P<0.05)。结论:转染DLC1基因可使OVCAR-3G1期细胞比例及凋亡率升高,对顺铂敏感性增加,该作用可能依赖于细胞内外源性DLC1基因的表达、p-FAK表达降低和p-p38表达增强。
文摘目的：探讨乳腺癌中肝癌缺失基因1（deleted in liver Cancer-1，DLC1）和DLC1-mRNA的表达及其临床意义。方法：应用原位杂交技术和免疫组织化学EnVision二步法，检测52例乳腺浸润性导管癌和42例非癌乳腺组织（包括癌旁乳腺组织20例和乳腺纤维腺瘤22例）中DLC1和DLC1-mRNA的表达，分析乳腺癌中DLC1和DLC1-mRNA的表达与患者年龄、肿瘤最大直径、组织学分级、腋窝淋巴结转移和TNM分期等临床病理参数的相关性。结果：DLC1和DLC1-mRNA在乳腺癌和非癌乳腺组织中的阳性表达率分别为（57．7％，50．0％）和（92．9％，90．5％），DLC1和DLC1-mRNA在乳腺癌中的表达率显著低于非癌乳腺组织（χ^2=14．717，P=0．000；χ^2=17．518，P=0．000），差异均有显著统计学意义（P〈0．001）。乳腺癌中DLCI和DLC1-mRNA的表达与组织学分级（L=-0．811，P=0．000；rs=-0．422，P〈0．05）、腋淋巴结转移（rs=0．410，P〈0．01；rs=-0．445，P〈0．01）和TNM分期（rs=-0．319，P〈0．05；rs=-0．405，P〈0．05）均呈负相关；DLCI—mRNA的表达与肿瘤最大直径（rs=-0．347，P〈0．05）亦呈负相关。DLC1与肿瘤最大直径（rs=0．073）和DLC1、DLC1-mRNA的表达与患者年龄（rs=0．077；rs=0．008）的相关性均无统计学意义（P〉0．05）。结论：DLC1蛋白和DLC1-mRNA在乳腺癌中呈低表达或失表达，在乳腺癌的恶性演进中扮演着重要角色。检测乳腺癌中DLC1和DLC1-mRNA的表达，结合相关临床病理参数，可作为判断乳腺癌生物学行为和预后的一个参考指标。
