Comparisons of voided urine cytology, nuclear matrix protein-22 and bladder tumor associated antigen tests for bladder cancer of geriatric male patients in Taiwan, China

Aim： To compare the results of bladder tumor associated antigen （BTA TRAK）, nuclear matrix protein 22 （NMP 22） and voided urine cytology （VUC） in detecting bladder cancer. Methods： A total of 135 elderly male and 50 healthy volunteers enrolled in this study were classified into three groups： （i） 93 patients with bladder cancer; （ii） 42 patients with urinary benign conditions; and （iii） 50 healthy volunteers. BTA TRAK and NMP 22 kits were used to detect bladder cancer. Voided urine cytology was used to compare the sensitivity and specificity of the screening tests. Results： The sensitivity and specificity of cytology, BTA TRAK and NMP 22 were 24% and 97%, 51% and 73%, 78% and 73%, respectively. The level of NMP 22 increased with tumor grading. The BTA TRAK kit has the lowest sensitivity among the screening tests. The NMP 22 with the best sensitivity can be an adjunct to cytology for evaluating bladder cancer. Conclusion： The NMP 22 test has a better correlation with the grading of the bladder cancer than BTA TRAK. As cytology units are typically not available in hospitals or in outpatient clinics, NMP 22 might be a promising tool for screening bladder cancer.

Significance of age and comorbidity as prognostic indicators for patients with bladder cancer

The aim of this study was to determine the impact that age and comorbidity status have on both overall and bladder cancer-specific survival of bladder cancer patients. We obtained medical information pertaining to a population of 528 patients with newly diagnosed bladder cancer from Chung-Ang University Hospital cancer registry. The Adult Comorbidity Evaluation-27 （ACE-27） test, which has been previously validated in adult cancer patients, was used to assess comorbidity. We evaluated differences in the demographic and clinical characteristics of included patients, as well as differences in the treatments they received after categorizing them by age. The median age at the time of bladder cancer diagnosis of the entire cohort was 63 years, and the median follow-up time was 97 months. Of the 528 patients who were included in our study, 303 had at least one comorbid condition and 249 died during the follow-up period. When patients were stratified by age, we found that older patients had a higher proportion of severe comorbidities （P 〈 0.01） than younger patients, and that a lower proportion of them underwent radical cystec- tomy for invasive bladder cancer （IBC） （P 〈 0.01）. By multivariate analysis, we found that older age was predictive of lower overall survival （OS） and bladder cancer-specific survival （BCSS） rates among patients with superficial bladder cancer （SBC） and of lower OS rates among patients with IBC. We also found that moderate-severe comorbidity status and treatment through a bladder-conserving approach were predictive of lower OS and cancer-specific survival rates among patients with IBC. The disparity between overall deaths and bladder cancer deaths was shown in SBC and increased along with age and higher comorbidity. Age and comorbidity were found to be independent predictive factors of OS and BCSS among bladder cancer patients, and explained the disparity that we observed between overall bladder cancer-specific mortality rates.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

Objective： To study the pathologic features of plasmacytoid transitional cell carcinoma of the bladder, and to analyze the diagnostic features, criteria for differential diagnosis and the clinical significance of the tumor. Methods： Two cases of bladder plasmacytoid transitional cell carcinoma were studied. Routine paraffin sections with HE staining, Pap smear and immunohistochemistry by S-P method were observed under a light microscope. Pathological and clinical data were analyzed by comparison with early reported cases in literatures. Results： A characteristic feature of this tumor was of deep invasion in the lamina propria and/or muscularis propria, in addition to the component of carcinoma in situ in the mucosa, when tumors were diagnosed. The histological pattern and cytological features showed similarity to a plasmacytoid tumor. The tumor cells were strongly positive for AE1/AE3, CEA and CK18. The prognosis appeared to be worse than ordinary transitional cell carcinoma. Conclusion： The plasmacytoid transitional cell carcinoma of bladder is rare but has typical pathological, immunohistological and clinical features. Pathologists should be aware of this kind of primary tumor of bladder.

Clinical significance of elevation of serum CA125 level in patients with metastatic bladder carcinoma

Objective： To explore the clinical significance of the examination of serum CA125 level of patients with metastatic bladder carcinoma. Methods： Electrochemiluminescence technique was used to examine the serum CA125 concentration of 58 cases with metastatic bladder cancer. 30 cases of superficial bladder cancer and 8 cases of other urological diseases were collected as the control group. Results： Serum CA125 level in 39 （67.2%） out of 58 cases ranged from 36.7 U/mL to 1485.6 U/mL （mean 496.3 U/mL）, being higher than normal （〈 35 U/mL）. Serum CA125 level of metastatic bladder cancer patients was 324.5 U/mL, significantly higher than that in control group （P 〈 0.001）. Serum CA125 level of 10 patients after transurethral resection operation was significantly lower than that before operation （P 〈 0.05）. Serum CA125 level of 16 patients who refused further treatment significantly increased from 450.4 U/mL, to 505.8 U/mL （P = 0.041） 3 months after discharge from the hospital. Serum CA125 level of 17 patients significantly decreased from 475.8 U/L to 237.9 U/mL （P 〈 0.001 ） after bilateral iliac-artedal embolism treatment. Conclusion： CA125 may be a valuable marker for the judgment of advanced metastatic bladder cancer.

Clinicopathologic Observation of 6 Cases with Neuroendocrine Carcinoma of the Urinary Bladder

OBJECTIVE To discuss the pathologic characteristics and theprognosis of neuroendocrine carcinoma of the bladder(NECB)in order to assist in making a precise diagnosis and to effectivelytreat the disease.METHODS Clinicopathologic features of the 6 cases with NECBwere analyzed retrospectively.The personal data of the patientsand the pathologic and immunohistochemical characteristics ofthe tumor were investigated.The follow-up of these patients wasconducted over a time period ranging from 3 months to 9 years.RESULTS Transurethral resection of the bladder tumorwas performed in all 6 patients.Based on the results of thepathologic examination,4 of the cases were diagnosed as smallcell neuroendocrine carcinoma and the other 2 were diagnosedas atypical carcinoid tumor.On immunohistochemical stainingall tumors expressed neuroendocrine markers includingneuronspecific enolase(CD56),synaptophysin(Syn)andchromogranin(CgA).In patients receiving partial cystectomyfollowed by postoperative chemotherapy,relapse was found in 4of the 6 cases on follow up.CONCLUSION NECB is a rare entity and a tumor with highmalignant potential and characteristic pathologic features.Hematuria is the cardinal symptom of NECB.Metastasis mayoccur at an early stage and the prognosis of the disease is poor.Final diagnosis of NECB depends on histopathologic examinationand immunohistochemical assays.Surgical excision combinedwith radiotherapy and chemotherapy is considered an effectivetreatment.

Caspase-3与Bcl-2蛋白在膀胱移行细胞癌中的表达及意义

背景和目的:肿瘤的发生是细胞异常增生和凋亡不足的结果。以往研究认为凋亡的发生与Caspase-3和Bcl-2蛋白有密切的联系。本研究拟通过检测Caspase-3和Bcl-2蛋白在膀胱移行细胞癌中的表达,探讨其在膀胱移行细胞癌发生、发展中的意义。方法:采用免疫组织化学(SP)法,对52例膀胱移行细胞癌组织和10例正常膀胱粘膜组织中的Caspase-3及Bcl-2蛋白表达情况进行检测。结果:膀胱移行细胞癌组织中的Caspase-3蛋白表达率(53.8%,28/52)明显低于正常膀胱粘膜组织(90.0%,9/10),Caspase-3的蛋白表达与膀胱移行细胞癌的病理分级有关(P<0.05),但与临床分期没有明显的联系;膀胱移行细胞癌组织中的Bcl-2蛋白表达率(51.9%,27/52)明显高于正常膀胱粘膜组织(20.0%,2/10),且Bcl-2蛋白表达情况与病理分级、临床分期均无关(P>0.05)。在正常膀胱粘膜中Caspase-3与Bcl-2的蛋白表达呈负相关(rs=-0.659,P<0.01)。结论:Caspase-3蛋白的高表达与Bcl-2蛋白的低表达在膀胱癌的发生和细胞凋亡的调控方面可能起着重要作用。

MMC诱导EJ细胞凋亡和Fas/FasL、Caspase-3基因表达

目的:研究丝裂霉素(MMC)在体外诱导膀胱癌细胞EJ凋亡和凋亡相关基因Fas/FasL、Caspase-3表达的关系。方法:以低剂量MMC(0.100mg/ml)诱导EJ细胞凋亡;以TUNEL法和FCM研究EJ细胞凋亡、细胞周期分布及Caspase-3抗体对抗MMC诱导凋亡;以免疫组化检测Fas/FasL、Caspase-3蛋白表达。结果:低剂量MMC处理的EJ细胞出现明显的凋亡形态特征,凋亡峰和细胞生长阻滞均发生于G0/G1期,Fas/FasL、Caspase-3蛋白呈上调表达,Caspase-3抗体能特异性阻断MMC诱导EJ细胞凋亡。结论:低剂量MMC能够诱导EJ细胞凋亡和增加Fas/FasL、Caspase-3基因表达,且与启动Caspase凋亡信号传导有关。

COX-2、u-PA和TSP-1在胃癌及周围淋巴结中的表达及意义

目的:研究COX-2、u-PA和TSP-1在胃癌及周围淋巴结中的表达状况,探讨它们在胃癌浸润和淋巴结转移中的作用和意义。方法:用组织芯片技术和免疫组化法检测COX-2、u-PA和TSP-1的表达。结果:COX-2、u-PA和TSP-1在胃癌组阳性表达率分别为67.7%、78.1%和78.6%,均显著高于对照组(40.0%、6.7%和40.0%,P<0.05)。COX-2表达与浸润深度有关(P<0.05)。u-PA表达与浸润深度和淋巴结转移均有关(P<0.05)。TSP-1表达与浸润深度和淋巴结转移均无关(P>0.05)。COX-2、u-PA和TSP-1在转移淋巴结和对应癌组织间的表达差异无显著性(P>0.05)。COX-2和u-PA、TSP-1的表达呈正相关,u-PA和TSP-1的表达无相关关系。结论:胃癌中COX-2、u-PA和TSP-1高表达;COX-2表达与胃癌的浸润深度有关,u-PA表达与浸润深度和淋巴结转移有关。

EPAS1、VEGF在胰腺癌中表达及其相关性

目的研究胰腺癌组织中缺氧诱导因子2(EPAS1/HIF-2α)、血管内皮生长因子(VEGF)和微血管密度(MVD)的表达及与临床病理特征之间的关系。方法应用逆转录聚合酶链反应(RT-PCR)、免疫印迹Western blot、免疫组化SP法检测60例胰腺癌及相应正常胰腺组织中EPAS1、VEGF mRNA和蛋白的表达和分布,同时检测MVD作为判断血管生成的指标,分析其间的相关性以及与肿瘤临床病理特征之间的关系。结果EPAS1、VEGF和MVD在胰腺癌组织中的表达明显高于正常胰腺组织,VEGF在mRNA和蛋白水平均增高(P<0.01),但EPAS1只在蛋白水平增高(P<0.01)。此外,三者之间的表达具有显著相关性(P<0.01)。EPAS1和VEGF的阳性表达与胰腺癌的TNM分期、肿瘤大小有关。结论胰腺癌组织中EPAS1和VEGF呈过量表达,且EPAS1的表达与VEGF及MVD呈显著正相关。EPAS1可通过上调VEGF表达来促进胰腺癌血管生成从而在胰腺癌的发生、发展中起重要作用。

miR-216a-5p靶向作用于PAK2对膀胱癌细胞增殖和凋亡影响的体外研究

目的探讨miR-216a-5p在多种膀胱癌细胞系中表达及调控p21活化蛋白激酶2(PAK2)基因对膀胱癌细胞增殖和凋亡的影响。方法通过实时荧光定量聚合酶链反应(qRT-PCR)检测miR-216a-5p在正常膀胱细胞系SV-HUC-1及膀胱癌细胞系5637、J82、T24和EJ中的表达,选取其中两种表达miR-216a-5p最少的5637和J82为对象,实验分两组:对照组(转染miR-NC)、实验组(转染miR-216a-5p)。利用qRT-PCR法检测PAK2 mRNA的表达。Western blot法检测PAK2、p-Akt和p-ERK蛋白的表达。Cell Counting Kit-8(CCK-8)实验和克隆形成实验检测膀胱癌细胞活力和增殖能力。流式细胞术检测细胞凋亡情况。结果 miR-216a-5p在膀胱癌细胞系中的表达量均低。实验组PAK2基因mRNA及其蛋自的表达明显降低,PAK2 mRNA在5637细胞中对照组和实验组表达量分别为1.01±0.15和0.40±0.11(P<0.01),在J82细胞中对照组和实验组表达量分别为1.00±0.09和0.56±0.14(P<0.01)。p-Akt和p-ERK蛋白表达显著降低。实验组细胞活力明显被抑制,增殖能力明显降低。实验组细胞凋亡显著增加(P<0.01)。结论 miR-216a-5p在多种膀胱癌细胞系中呈低表达,可在体外靶向抑制PAK2基因,抑制膀胱癌细胞系5637和J82的增殖能力,促进细胞凋亡,可能成为具有膀胱癌生物治疗意义的靶标分子。

膀胱移行细胞癌组织中HPA、VEGF基因的表达及其意义

【目的】研究膀胱移行细胞癌（BTCC）组织中乙酰肝素酶（HPA）及血管内皮细胞生长因子（VEGFmRNA）的表达及其临床意义。【方法】应用RT—PCR技术检测62例BTCC组织中HPAmRNA及VEGF mRNA表达，并以12例正常膀胱组织作对照，分析HPAmRNA表达与肿瘤部分临床、病理学特征的关系，并分析HPA与VEGF表达的相关性。【结果】12例正常膀胱组织未发现HPAmRNA阳性表达，BTCC组织中HPAmRNA阳性表达率为58．06％（36／62）。其表达与肿瘤的病理分级、临床分期、淋巴结转移及复发明显相关。而且，HPA与VEGF二者的表达具有明显相关性（r=0．501，P〈0．01）。【结论]HPAmRNA阳性表达与BTCC侵袭转移密切相关，HPA在BTCC组织中过度表达可能通过释放VEGF促进肿瘤血管生成。

凋亡相关蛋白Livin及Caspase-3在膀胱移行细胞癌中的表达及临床意义

【目的】探讨凋亡相关蛋白Livin及Caspase-3在膀胱移形细胞癌(BTCC)中的表达及其临床意义。【方法】应用SP免疫组织化学法检测55例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Livin和Caspase-3表达的情况,结合临床资料进行分析,并探讨两者相关性。【结果】Livin在膀胱移形细胞癌标本中的表达阳性率为76.4%(42/55),而正常对照组中无一例呈阳性表达;Caspase-3在膀胱移行细胞癌标本中的表达阳性率为32.7%(18/55),与对照组阳性率90%(9/10)相比差异有统计学意义(P<0.05)。Livin的表达与膀胱移行细胞癌的初发和复发显著相关(P<0.05),但与组织学分级、临床病理分期、转移与否、肿瘤数目无关;Caspase-3的表达与膀胱移行细胞癌的初发复发、组织学分级、临床病理分期、转移与否、肿瘤数目均无关。相关性分析表明,膀胱移行细胞癌中的Livin表达与Caspase-3表达呈负相关。【结论】Livin蛋白与膀胱癌的发生和复发有关,可作为BTCC早期诊断和评判术后高复发风险的一项重要指标,且Livin的高表达和Caspase-3蛋白的低表达在膀胱移行细胞癌的发生发展起着重要作用。

PPAR-γ和PTEN蛋白在膀胱移行细胞癌中的表达及意义

目的测定膀胱移行细胞癌中PPAR-γ和PTEN蛋白的表达及与其病理分级、临床分期及预后相关性。方法免疫组织化学法检测PPAR-γ和PTEN于膀胱移行细胞癌标本及正常膀胱组织中的表达程度,病理分析仪测定蛋白表达程度。结果 (1)在正常膀胱组织中PPAR-γ蛋白的表达(20%)明显低于膀胱癌(68%),而正常膀胱组织PTEN蛋白的表达(100%)明显高于膀胱癌(52%),两者阳性率差异有统计学意义(P<0.05)。(2)膀胱移行细胞癌组织中PPAR-γ表达与临床分期、病理分期、淋巴结转移呈正相关性,PTEN蛋白表达呈负相关性。(3)PPAR-γ蛋白和PTEN蛋白在膀胱移行细胞癌中表达呈负相关关系(r=-0.604,P<0.05)。结论 PPAR-γ和PTEN可能参与了膀胱肿瘤的发生发展过程,对膀胱癌诊断、临床分期及预后有一定价值。

凋亡相关蛋白Fas及caspase-3在膀胱移行细胞癌中表达及临床意义

目的:探讨凋亡相关蛋白Fas及caspase-3在膀胱移行细胞癌中的表达及其临床意义。方法:应用SP免疫组织化学法检测45例膀胱移行细胞癌及10例正常膀胱黏膜组织石蜡切片中Fas和caspase-3表达的情况,并结合临床资料进行分析。结果:Fas在膀胱移行细胞癌标本中的表达阳性率为46.7%(21/45),而在正常对照组中阳性表达率为100%;caspase-3在膀胱移行细胞癌标本中的表达阳性率为37.8%(17/45),与对照组阳性率为90%(9/10)相比差异有统计学意义(P<0.05)。Fas的表达与膀胱移行细胞癌的组织学分级,初发和复发及肿瘤数目之间差异有统计学意义(P<0.05),但与临床病理分期无关;Caspase-3的表达与膀胱移行细胞癌的初发和复发相关(P<0.05),但与组织学分级,肿瘤数目,临床分期均无关。相关性分析表明,膀胱移行细胞癌中Fas的表达与caspase-3表达呈正相关。结论:Fas在膀胱癌组织中选择性表达降低且与膀胱移行细胞癌的分化程度密切相关的,caspase-3蛋白在膀胱移行细胞癌中表达下降,因此Fas及caspase-3蛋白对于判断膀胱移行细胞癌预后有重要临床指导意义。

莲心碱促进膀胱癌5637细胞凋亡增强Caspase-7表达及活化

目的研究莲心碱(Liensinine)对膀胱癌细胞株5637凋亡的影响,初步探讨其作用机制。方法使用CCK-8法及克隆形成实验检测莲心碱对5637细胞增殖的抑制作用;通过流式细胞术Annexin V-FITC/PI双染法测定莲心碱对5637细胞凋亡的影响;采用Western blot技术分析细胞凋亡相关基因Caspase-7表达状况。结果 CCK-8法及克隆形成实验结果均表明莲心碱对膀胱癌细胞5637增殖有明显的抑制作用,并呈剂量-效应关系。流式细胞术结果提示莲心碱可使膀胱癌5637细胞发生早期凋亡;Western blot检测结果显示莲心碱增强5637细胞Caspase-7表达并促进其活化。结论莲心碱可抑制5637细胞增殖,使其发生早期凋亡,其作用机制可能与促进Caspase-7表达及活化有关。

基质降解酶u-PA、PAI-1与人口腔鳞状细胞癌细胞侵袭转移的相关性研究

目的 探讨体外培养细胞系TSCCa和GNM细胞的u -PA及PAI - 1活性和表达与口腔鳞状细胞癌侵袭转移的关系。方法 采用酶联免疫反应法和免疫组化法测定了两细胞系中u -PA及PAI - 1的活性和表达 ,同时对GNM细胞在BALB/CA裸鼠皮下种植瘤组织的u -PA及PAI - 1抗原表达进行了测定。结果 两细胞系均能产生u -PA及PAI- 1,但u -PA在两细胞系中的表达不同 ,在GNM细胞u -PA为高表达 ,在TSCCa细胞中u -PA为低表达 ,PAI- 1在两细胞系中均为高表达 ;种植瘤组织中u -PA呈阳性～强阳性表达 ,PAI- 1为阴性表达。结论 u

凋亡抑制因子Survivin在膀胱癌中的表达与CPA血流的相关性研究

目的:探讨膀胱癌中凋亡抑制因子Survivin的表达与CPA血流的关系。方法:术前应用CPA检测50例膀胱癌患者及20例膀胱非肿瘤性增生患者的血流信号及其阻力指数RI,术后用免疫组化法测该组织中Survivin基因蛋白的表达。结果:50例膀胱癌患者的Survivin基因蛋白的阳性表达率(78%)显著高于非肿瘤性增生组(25%,P<0.05)。膀胱癌的Survivin基因蛋白的表达强度与CPA血流分级呈正相关(r=0.699,P<0.05),其RI值(0.50±0.43)明显低于非肿瘤性增生组(0.69±0.41,P<0.05),表达强度与RI值呈负相关(r=-0.545,P<0.05)。结论:Survivin基因蛋白在膀胱癌中呈高强度表达,其表达强度与CPA的血流分级呈正相关。两者的有机结合可在术前、术后对膀胱癌进行评估并为临床早期诊断及判断预后提供新的理论依据。

caspase-3、Ki-67在膀胱移行细胞癌中的表达及临床意义

目的:探讨凋亡同胱氨酸蛋白-3(caspase-3)、增殖细胞核抗原Ki-67在膀胱移行细胞癌(bladder transitional cell carcinomas,BTCC)的表达及其与肿瘤分级、分期之间的关系。方法:采用免疫组织化学SP法,对55例BTCC和10例正常膀胱黏膜caspase-3和Ki-67的表达进行检测,分析两者在膀胱癌组织和非膀胱癌组织中的表达及表达水平与BTCC病理学分级、临床分期的关系。结果:caspase-3在正常膀胱黏膜中的阳性表达率为90.0%,膀胱癌组织中的阳性表达率为47.3%,两者阳性表达率差异有统计学意义(P<0.05),同时发现caspase-3的阳性表达率随膀胱癌的组织分化程度的降低而表现出下降的趋势,差异有统计学意义(P<0.05)。Ki-67在正常膀胱黏膜中没有发现阳性表达病例,在膀胱癌中的阳性表达率为52.7%,差异有统计学意义(P<0.01),Ki-67的阳性表达率随肿瘤组织分化程度的降低和临床分期的增高表现出上升趋势,且差异有统计学意义(P<0.05)。结论:caspase-3参与了BTCC的发生过程,可以作为评价BTCC侵袭性的一个指标。Ki-67的阳性表达率增高与BTCC的发生、发展可能有一定关系。

5-氮-2′-脱氧胞苷对人膀胱癌细胞系T_(24)细胞及其Apaf-1、APC基因甲基化状况的影响

目的观察5-氮-2′-脱氧胞苷(5-Aza-CdR)对人膀胱癌T24细胞增殖、凋亡的影响及其对凋亡蛋白酶活化因子-1(Apaf-1)、结肠腺瘤性息肉病(APC)基因甲基化表达状况的影响。方法应用不同浓度的5-Aza-CdR处理人膀胱癌T24细胞,四甲基偶氮唑盐(MTT)比色法检测细胞生长抑制率;流式细胞术(FCM)检测细胞周期和凋亡的变化情况;以甲基化特异性PCR方法(MSP法)检测膀胱癌T24细胞株中Apaf-1及APC基因的甲基化状态。结果膀胱癌T24细胞中Apaf-1、APC基因分别呈半甲基化及高甲基化,5-Aza-CdR作用后T24细胞中Apaf-1及APC基因启动子区域均呈去甲基化状态;T24细胞的生长受到明显抑制,0.50、1.00、2.50、5.00μmol/L 5-Aza-CdR作用T24细胞72h后,细胞生长抑制率分别为0.50%、5.40%、20.40%、23.00%,组间比较差异有统计学意义(P<0.05),呈剂量和时间依赖关系。72h后G0/G1期的比例增加,S期比例明显减少,细胞凋亡率明显增加,5.00μmol/L 5-Aza-CdR组凋亡率为(40.35±3.63)%,对照组为(8.17±1.52)%,组间比较差异有统计学意义(P<0.01)。结论 5-Aza-CdR能逆转膀胱癌T24细胞中的Apaf-1及APC基因甲基化,恢复该基因的表达,诱导膀胱癌T24细胞凋亡。

hepaCAM基因缺失突变体对膀胱癌细胞的生物学影响

目的:探讨hepaCAM基因细胞外结构缺失突变体对膀胱癌细胞的生物学影响。方法:采用脂质体法将hepaCAM缺失突变体转染T24细胞;激光共聚焦显微镜检测突变体蛋白细胞定位;Western印迹法检测蛋白的表达;体外黏附、解离实验及伤口愈合、基质胶侵袭实验研究突变体对T24细胞黏附、活动力的影响;MTT法检测对细胞增殖的改变。结果:突变体蛋白在单个细胞中的分布与野生型hepaCAM蛋白相近,定位于细胞核周边区域,但细胞相互连接后,与野生型hepaCAM蛋白定位不同,突变体蛋白呈现非特异性分布。获得稳定表达突变体蛋白的T24细胞,在细胞黏附、活动力方面明显低于表达野生型hepaCAM蛋白组,细胞增殖与表达野生型hepaCAM蛋白组相比明显增强。结论:缺失细胞外区域对hepaCAM蛋白细胞定位有重要影响,对抑制T24细胞增殖、增强细胞黏附及活动力无明显作用。细胞外区域对hepaCAM基因发挥正常作用是必须的。