目的:探讨DNAJ热激蛋白家族B8基因(DNAJ heat shock protein family member B8,DNAJB8)在肺腺癌组织中的表达及其对肺腺癌细胞侵袭转移的作用和可能机制。方法:收集四川省人民医院2006年至2008年的肺腺癌手术切除标本102例,通过免疫组...目的:探讨DNAJ热激蛋白家族B8基因(DNAJ heat shock protein family member B8,DNAJB8)在肺腺癌组织中的表达及其对肺腺癌细胞侵袭转移的作用和可能机制。方法:收集四川省人民医院2006年至2008年的肺腺癌手术切除标本102例,通过免疫组织化学(IHC)实验检测DNAJB8在肺腺癌组织中的表达情况,并分析其与临床病理参数及预后的关系。构建DNAJB8稳定敲低的肺腺癌A549细胞和DNAJB8稳定过表达的肺腺癌H1299细胞,CCK-8实验检测DNAJB8敲降或过表达对肺腺癌细胞增殖的影响,Transwell法检测其对肺腺癌细胞侵袭能力的影响,Western blotting检测其对肺腺癌细胞内侵袭相关蛋白MMP-2、MMP-9和ERK表达及活性的影响。裸鼠尾静脉注射DNAJB8稳定敲低的A549细胞构建肺腺癌转移模型,观察DNAJB8对A549细胞体内转移能力的影响。结果:DNAJB8在肺腺癌组织中的表达明显高于正常肺组织,其高表达与患者的淋巴结转移及TNM分期呈正相关,并且预示着患者有较差的预后(均P<0.01)。DNAJB8在A549细胞中的表达量高于H1299细胞,下调DNAJB8表达能够抑制A549细胞的侵袭[(41±3)vs(192±11)个,P<0.01],而上调DNAJB8的表达能够促进H1299细胞的侵袭[(235±14)vs(25±4)个,P<0.01]。实验组肺腺癌转移模型裸鼠肺脏肿瘤结节数显著低于对照组[(5±1)vs(17±3)个,P<0.01]。A549细胞中DNAJB8敲降后,MMP-2、MMP-9表达量和p-ERK水平均显著下降(均P<0.01);而H1299细胞高表达DNAJB8后,MMP-2、MMP-9表达量和p-ERK水平均显著升高(均P<0.01)。结论:DNAJB8能够促进肺腺癌的侵袭和转移,其机制可能与MEK/Erk信号通路有关。展开更多
Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic op...Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic option,and the recurrence rate is extremely high(>50%within 3 years).A newly discovered chromosomal deletion that occurs in the majority of FLCs generates a novel kinase fusion between DnaJ heat shock protein family member B1(DNAJB1)and protein kinase cAMP-activated catalytic subunit alpha(PRKACA)(DNAJB1-PRKACA).Despite its high penetrance and apparent specificity for FLC,the oncogenic role of this fusion event remains unclear.In this review article,we discuss the histology,presentation and diagnosis,current treatment,and roles of the DNAJB1-PRKACA as well as research models contributing to our understanding of this disease.展开更多
文摘目的:探讨DNAJ热激蛋白家族B8基因(DNAJ heat shock protein family member B8,DNAJB8)在肺腺癌组织中的表达及其对肺腺癌细胞侵袭转移的作用和可能机制。方法:收集四川省人民医院2006年至2008年的肺腺癌手术切除标本102例,通过免疫组织化学(IHC)实验检测DNAJB8在肺腺癌组织中的表达情况,并分析其与临床病理参数及预后的关系。构建DNAJB8稳定敲低的肺腺癌A549细胞和DNAJB8稳定过表达的肺腺癌H1299细胞,CCK-8实验检测DNAJB8敲降或过表达对肺腺癌细胞增殖的影响,Transwell法检测其对肺腺癌细胞侵袭能力的影响,Western blotting检测其对肺腺癌细胞内侵袭相关蛋白MMP-2、MMP-9和ERK表达及活性的影响。裸鼠尾静脉注射DNAJB8稳定敲低的A549细胞构建肺腺癌转移模型,观察DNAJB8对A549细胞体内转移能力的影响。结果:DNAJB8在肺腺癌组织中的表达明显高于正常肺组织,其高表达与患者的淋巴结转移及TNM分期呈正相关,并且预示着患者有较差的预后(均P<0.01)。DNAJB8在A549细胞中的表达量高于H1299细胞,下调DNAJB8表达能够抑制A549细胞的侵袭[(41±3)vs(192±11)个,P<0.01],而上调DNAJB8的表达能够促进H1299细胞的侵袭[(235±14)vs(25±4)个,P<0.01]。实验组肺腺癌转移模型裸鼠肺脏肿瘤结节数显著低于对照组[(5±1)vs(17±3)个,P<0.01]。A549细胞中DNAJB8敲降后,MMP-2、MMP-9表达量和p-ERK水平均显著下降(均P<0.01);而H1299细胞高表达DNAJB8后,MMP-2、MMP-9表达量和p-ERK水平均显著升高(均P<0.01)。结论:DNAJB8能够促进肺腺癌的侵袭和转移,其机制可能与MEK/Erk信号通路有关。
文摘Fibrolamellar hepatocellular carcinoma(FLC)is a rare but aggressive liver cancer of children that occurs predominantly in teenagers without a history of liver disease.Surgical resection remains the only therapeutic option,and the recurrence rate is extremely high(>50%within 3 years).A newly discovered chromosomal deletion that occurs in the majority of FLCs generates a novel kinase fusion between DnaJ heat shock protein family member B1(DNAJB1)and protein kinase cAMP-activated catalytic subunit alpha(PRKACA)(DNAJB1-PRKACA).Despite its high penetrance and apparent specificity for FLC,the oncogenic role of this fusion event remains unclear.In this review article,we discuss the histology,presentation and diagnosis,current treatment,and roles of the DNAJB1-PRKACA as well as research models contributing to our understanding of this disease.