卵巢上皮性肿瘤中Skp2、p27kipl、E-cad的表达

目的检测Skp2、p27kipl和E-cad在卵巢上皮性肿瘤中的表达情况及其相互关系。方法采用免疫组化SP法，检测99例卵巢上皮性肿瘤组织中Skp2、p27kipl及E-cad的表达。结果p27kipl在卵巢良性肿瘤、交界性肿瘤的表达率分别为76．5％、70．6％高于卵巢癌29．2％（P〈0．05），在早期癌中的表达高于晚期癌（P〈0．05）。Skp2在卵巢良性肿瘤、交界性肿瘤的表达率分别为0、23．5％，均低于卵巢癌50．8％（P〈0．05），在早期癌的表达低于晚期癌（P〈0．05）。卵巢癌中skp2表达与组织分化有关，在低分化癌的阳性表达率高于高分化癌（P〈0．05），在组织学类型方面，浆液性癌中skp2的阳性表达率高于非浆液性癌（P〈0．05）。E—cad在良性肿瘤、交界性肿瘤和卵巢癌表达率分别为88．2％、82．4％、55．4％，恶性组低于良性组（P〈0．05）。E—cad在早期癌的表达率高于晚期癌（P〈0．05）。Skp2表达与p27kipl表达呈负相关（P〈0．05），E-cad表达与p27kipl表达呈正相关（P〈0．05），而E-cad表达与Skp2表达则呈负相关（P〈0．05）。结论skp2过度表达与p27kipl表达减少可能与卵巢上皮性肿瘤的发生发展密切相关，而E-cad在晚期卵巢癌中表达降低可能反映了卵巢癌分化程度的降低。     

大肠癌上皮型钙粘蛋白表达及其与浸润转移的关系

目的　探讨上皮型钙粘蛋白 (E cad)表达与大肠癌 (CLI)浸润转移的关系。方法　选取 6 0例原发性CLI组织及相应癌旁正常组织 ,用免疫组化SP法和抗E cad抗体检测观察E cad的表达。结果　CLI组织中E cad总阳性率 55% ,正常大肠上皮组织全部表达 ,E cad的表达与癌组织分化程度、生长方式、浸润深度、淋巴结转移密切相关 (P <0 .0 1)。结论　CLI组织E cad丧失或低表达是其获得浸润转移能力的因素之一。E cad可作为一种新的CLI标志物 ,其表达对判断预后有一定价值     

前列腺癌组织中ILK和E-Cadherin的表达及其意义

目的　探讨整合素连接激酶 (ILK )、上皮细胞钙黏素 (E cad)在前列腺癌组织中的表达及其意义。方法　应用免疫组织化学 (S P)方法检测 5 0例前列腺癌及 16例良性前列腺增生组织中ILK、E cad蛋白的表达。结果　前列腺癌组织中ILK、E cad阳性表达率分别为 46.0 % (2 3 /5 0 )、5 0 .0 % (2 5 /5 0 )。随肿瘤细胞病理分级、临床分期程度的增高 ,ILK阳性表达率增高而E cad表达降低 ,各组间均有显著性差异 (P <0 .0 5或P <0 .0 1)。与良性前列腺增生组织中的阳性表达率 10 0 .0 % (16/16)和 6.2 % (1/16)比较 ,均有显著性差异 (P <0 .0 5 )。结论　ILK、E cad蛋白异常表达在前列腺癌的恶性进展中起重要作用 ,ILK高表达或激活可能是E cad低表达或缺失的原因之一 ,联合检测ILK、E cad表达有利于判断病期及预后。     

Combined analysis of E-cadherin gene (CDH1) promoter hypermethylation and E-cadherin protein expression in patients with gastric cancer: implications for treatment with demethylating drugs.

BACKGROUND: Hypermethylation is studied as a new, relevant mechanism for silencing tumor suppressor genes. It is a potentially reversible epigenetic change and it is the target of novel anticancer compounds with demethylating activity. In this perspective, we investigated E-cadherin gene (CDH1) promoter hypermethylation in gastric carcinomas and its correlation with E-cadherin protein expression. METHODS: Consecutive cases of gastric carcinoma with assessable paraffin-embedded tumor blocks and paired normal mucosa were considered eligible for study entry. CDH1 promoter hypermethylation and E-cadherin protein expression were determined by methylation-specific polymerase chain reaction and immunohistochemistry, respectively. RESULTS: CDH1 promoter hypermethylation was found in 20 out of 70 gastric carcinomas and the epigenetic change occurred in the early, as well as in the locally advanced disease. In five cases, hypermethylation was also detected in the normal mucosa. Eighteen out of 20 hypermethylated tumors were of the diffuse histotype (P=0.0001). Of 24 tumors with reduced or negative E-cadherin expression, 19 were hypermethylated and 5 were unmethylated (P=0.0001). CONCLUSIONS: CDH1 promoter hypermethylation frequently occurs in gastric carcinomas of the diffuse histotype and it is significantly associated with downregulated E-cadherin expression. The knowledge on the hypermethylation status of tumor suppressor genes may be relevant to the development of demethylating drugs and novel chemopreventive strategies in solid tumors.     

钙粘附素及连环素表达与乳腺癌转移及预后的关系

目的:了解乳腺癌E-钙粘附素、连环素-α,-β的表达改变与转移及预后的关系。方法:采用免疫组织化学染色、病理组织学,对105例乳腺癌患者术后定期随访,统计学分析。结果:105例乳腺癌三种粘附分子组化染色减弱和消失频率为E-钙粘附素56%,连环素-α64%,连环素-β43%,与正常及非典型增生组差别明显,P值均小于0.001。单因素分析未能找到E-钙粘附素与转移及预后的联系,但证明连环素-α和-β表达下降分别与癌分化程度及与转移、预后相关,P<0.05和P<0.01。三种粘附分子中E-钙粘附素与连环素-α的表达有平行关系,双阳性组的转移率明显低于一种蛋白表达下降组,P<0.05。COX多因素分析三种粘附蛋白表达均未能成为独立影响乳腺癌预后的因素。结论:E-钙粘附素、连环素-α,-β表达的免疫组化反应在乳腺癌呈下降的总趋势,E-钙粘附素与连环素-α的表达有平行关系,双阳性者转移率明显低。在三者之中连环素-β表达下降与癌转移及病程进展有明显相关性,预后相对差。在考虑用细胞间粘附体系为判断乳腺癌预后指标时必须对该三种分子作综合检测。     

上皮型钙粘蛋白与大肠癌临床病理因素的关系

目的探讨上皮型钙粘蛋白（Ｅ一ｃａｄｈｅｒｉｎ,Ｅ－ＣＤ）在大肠癌中的表达与其临床病理因素的关系。方法采用免疫组织化学的方法研究大肠癌组织标本Ｅ－ＣＤ的表达情况。结果Ｅ－ＣＤ在正常大肠粘膜上皮组织均保留表达;而在大肠癌标本中的保留表达率为６６.７％ （７０／１０５）。结论与其它肿瘤相比较,Ｅ－ＣＤ在大肠癌中的减弱表达率较低,但是Ｅ－ＣＤ的减弱表达与大肠癌患者的年龄、病理组织学分化程度、临床Ｄｕｋｅｓ分期有显著的相关性,可以作为肿瘤预后的一个指标。     

乳腺癌组织中E-cadherin的表达与外周血微转移的相关性及临床意义

目的检测乳腺癌组织中E-cadherin的表达及患者外周血微转移的发生,探讨二者的相互关系及临床意义.方法应用逆转录-聚合酶链反应（RT-PCR）分别检测15例乳腺良性肿瘤患者及60例乳腺癌患者外周血CK-20及乳腺组织中E-cadherin mRNA的表达.结果 15例乳腺良性肿瘤组织中,均有E-cadherin阳性表达（100%）,而60例乳腺癌组织中,E-cadherin阳性表达23例（38.3%）,二者差异显著（P〈0.01）;CK-20在乳腺良性肿瘤患者外周血中未见表达.在60例乳腺癌患者外周血中,检出CK-20阳性表达28例（46.7%）,E-cadherin在相应癌组织中的阳性表达率为14.3% （4/28）,32例外周血CK-20阴性的乳腺癌病例中,E-cadherin的阳性表达率为59.3%（19/32）,二者差异显著（P〈0.01）.结论乳腺癌组织中E-cadherin的低表达与外周血高转移率显著相关,提示E-cadherin的表达缺失或低表达可能是导致乳腺癌高转移的因素之一,可作为临床判断预后的参考指标.     

MET receptor is a potential therapeutic target in high grade cervical cancer

Cervical cancer is one of the leading causes of death among women suffering from tumors. Current treatment options are insufficient. Here, we investigated the MET receptor as a potential molecular target in advanced cervical cancer. Downregulation of MET receptor expression via RNA interference in different cervical carcinoma cell lines dramatically decreased tumor growth and forced tumor differentiation in vivo. MET receptor silencing also led to a dramatic decrease in cell size and a decrease in proliferation rate under normal and stress conditions. MET receptor downregulation also resulted in decreased cyclin D1 and c-myc levels but did not increase apoptosis. Subsequent experiments showed that downregulation of the MET receptor decreased the expression of a key regulator of the epithelial-to-mesenchymal transition, SLUG. and increased the expression of E-cadherin, a hallmark of the epithelial phenotype. Moreover, MET downregulation impairs expression and signaling of CXCR4 receptor, responsible for invasive phenotype.Taken together, our results strongly suggest that the MET receptor influences the oncogenic properties of cervical carcinoma cells in vitro and in vivo. These findings highlight a unique role of the MET receptor in cervical carcinoma cells and indicate the MET receptor as a potential therapeutic target for advanced cervical carcinoma.     

Elevated Src family kinase activity stabilizes E-cadherin-based junctions and collective movement of head and neck squamous cell carcinomas

EGF receptor (EGFR) overexpression is thought to drive head and neck carcinogenesis however clinical responses to EGFR-targeting agents have been modest and alternate targets are actively sought to improve results. Src family kinases (SFKs), reported to act downstream of EGFR are among the alternative targets for which increased expression or activity in epithelial tumors is commonly associated to the dissolution of E-cadherin-based junctions and acquisition of a mesenchymal-like phenotype. Robust expression of total and activated Src was observed in advanced stage head and neck tumors (N=60) and in head and neck squamous cell carcinoma lines. In cultured cancer cells Src co-localized with E-cadherin in cell-cell junctions and its phosphorylation on Y419 was both constitutive and independent of EGFR activation. Selective inhibition of SFKs with SU6656 delocalized E-cadherin and disrupted cellular junctions without affecting E-cadherin expression and this effect was phenocopied by knockdown of Src or Yes. These findings reveal an EGFR-independent role for SFKs in the maintenance of intercellular junctions, which likely contributes to the cohesive invasion E-cadherin-positive cells in advanced tumors. Further, they highlight the need for a deeper comprehension of molecular pathways that drive collective cell invasion, in absence of mesenchymal transition, in order to combat tumor spread.     

Anxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells with high lymph node metastasis potential preferentially via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) and E-cadherin

ObjectiveAnnexin A5 (Anxa5) is associated with the progression of some cancers, while its role and regulation mechanism in tumor lymphatic metastasis is rarely reported. This study aims to investigate the influence of Anxa5 knockdown on the malignant behaviours of murine hepatocarcinoma Hca-F cell line with high lymph node metastatic (LNM) potential and the underlying regulation mechanism.MethodsRNA interfering was performed to silence Anxa5 in Hca-F. Monoclonal shRNA-Anxa5- Hca-F cells were obtained via G418 screening by limited dilution method. Quantitative real-time RT-PCR (qRT-PCR) and Western blotting (WB) were applied to measure Anxa5 expression levels. CCK-8, Boyden transwell-chamber and in situ LN adhesion assays were performed to explore the effects of Anxa5 on the proliferation, migration, invasion and adhesion capacities of Hca-F. WB and qRT-PCR were used to detect the level changes of key molecules in corresponding signal pathways.ResultsWe obtained two monoclonal shRNA-Anxa5-transfected Hca-F cell lines with stable knockdowns of Anxa5. Anxa5 knockdown resulted in significantly reduced proliferation, migration, invasion and in situ LN adhesion potentials of Hca-F in proportion to its knockdown extent. Anxa5 downregulation enhanced E-cadherin levels in Hca-F. Moreover, Anxa5 affected Hca-F behaviours specifically via ERK2/p-ERK2/c-Jun/p-c-Jun(Ser73) instead of p38MAPK/c-Jun, Jnk/c-Jun and AKT/c-Jun pathways.ConclusionsAnxa5 mediates the in vitro malignant behaviours of murine hepatocarcinoma Hca-F cells via ERK2/c-Jun/p-c-Jun(Ser73) and ERK2/E-cadherin pathways. It is an important molecule in metastasis (especially LNM) and a potential therapeutic target for hepatocarcinoma.