Metastasis-associated protein S100A4--a potential prognostic marker for colorectal cancer

BACKGROUND AND OBJECTIVES: Expression of S100A4, a small calcium-binding protein, in breast, oesophagus and gall bladder cancers is shown to be associated with adverse clinical outcome. We retrospectively examined the correlation of S100A4 expression and outcome in patients with colorectal cancer. METHODS: Tissue sections from 54 patients with Dukes B, C and D cancers operated on between 1995 and 1998 were stained with anti-S100A4 antibody. The S100A4 expression profile was correlated to the clinico-pathological details. RESULTS: There were 31 males and 23 females (mean age 65.94 years +/- 12.29). Dukes stage, >4 positive lymph node status and S100A4 expression were significantly associated with poorer survival. The 3 years survival of patients whose tumour stained positive for S100A4 was 62.85% compared to 93.75% for those stained negative (P < 0.012). In patients with <4 involved nodes, S100A4 expression led to poorer survival (57 months vs. 74 months; P < 0.0052). Within a particular Dukes stage, S100A4 expression was associated with poorer outcome. The 5 years survival of Dukes B patients whose tumour stained negative for S100A4 was 92% compared to 54.6% for those with positive tumours. CONCLUSION: Our results suggest that S100A4 expression is associated with adverse clinical outcome. Inclusion of S100A4 expression status may enhance our accuracy to prognosticate in patients with colorectal cancer.     

S100A4蛋白表达与胃癌侵袭转移关系的研究

目的：探讨Ｓ１００Ａ４蛋白产与胃癌侵袭转移的关系。方法：应用免疫组织化学方法检测６２例胃癌患者的胃癌组织和３８例癌旁正常粘膜、２３例淋巴结转移癌及胃癌纱ＭＫＮ４５、ＢＧＣ８２３中Ｓ１００Ａ４蛋白表达,Ｂｏｙｄｅｎ小室法检测胃癌细胞侵袭能力。结果：胃癌组织Ｓ１００Ａ４表达阳性率（７０．５９％）显著高于癌旁正常粘膜（１５．７９％）（Ｐ〈０．０１）。在弥温生长、低分化及未分化型、浸透浆膜、淋巴结转移阳性     

结肠癌组织中S100A4基因的表达及其意义

目的:检测S100A4基因在结肠癌细胞系及结肠癌组织中的表达,探讨其与结肠癌的关系。方法:运用RT-PCR法检测不同结肠癌细胞系S100A4基因的表达;选取结肠癌及其相应癌旁组织各61例,通过原位杂交方法检测S100A4基因的表达。结果:S100A4基因在癌旁正常结肠组织中不表达,而在结肠癌中阳性率为34.4%,明显增高,P<0.05。在存在淋巴结转移的患者中16例(55.2%)S100A4基因阳性表达,而在无淋巴结转移者中只有5例(15.6%)阳性,P=0.001。Dukes分期A期的4例患者表达均为阴性,B期25例患者中3例(12.0%)阳性,C期15例患者中7例(46.7%)阳性,D期17例患者中11例(64.7%)阳性。此外,肿瘤长径>3cm、大体病理分型为隆起型以及病理分级差的患者,S100A4基因阳性率较高,但是差异无统计学意义,P>0.05。结肠癌中S100A4基因表达增高,S100A4的表达与肿瘤的临床分期和淋巴结转移密切相关。临床分期晚及伴有淋巴结转移的患者S100A4基因表达明显增高。结论:S100A4基因与肿瘤的侵袭及转移密切相关,是判断结肠癌生物学行为及预后的有价值指标。     

S100A4蛋白在结肠腺瘤和结肠癌中的表达

[目的]探讨S100A4蛋白在结肠腺瘤和结肠癌中的表达及其临床意义。[方法]用免疫组化法检测S100A4在15例正常肠黏膜、80例结肠腺瘤和60例结肠癌中的表达。[结果]S100A4蛋白在正常肠黏膜中无表达,在结肠腺瘤中阳性率为16.25%,在结肠癌中阳性率为56.67%。[结论]S100A4与结肠腺瘤和结肠癌的发生发展密切相关,是预测结肠肿瘤进展的有用指标。     

Metastasis-associated protein S100A4 and p53 predict relapse in curatively resected stage III and IV (M0) gastric cancer

Purpose: Pathologic stage is the most important predictive factor of relapse in gastric cancer after curative resection. However, patients with the same stage often have different risks of relapse. Here, we investigated whether the expressions of molecular markers can supplement the current staging system in terms of relapse prediction. Patients and Methods: One hundred and nine stage III or IV (M0) patients who had received curative gastrectomy followed by adjuvant 5-fluorouracil and cisplatin chemotherapy were included in this study. The expressions of molecular markers including p53, p27, COX-2, HER-2, EGFR, maspin, S100A4, E-cadherin, Sp1, and p97 were analyzed by immunohistochemistry in cancer and paired normal tissues. Results: The overall relapse rate was 58.7%, and pathologic stage was a significant predictive factor of relapse (42% in stage IIIA, 48% in IIIB, 76% in IV, p = 0.005). Of the 10 markers examined, p53 and S100A4 were expressed only in tumor tissues, and S100A4 expression was significantly associated with a higher relapse rate (85% vs. 53%, p = 0.008). In multivariate analysis including tumor stage, S100A4 and p53 expression were independent predictive factors of relapse (relative risk, 6.98; 95% confidence interval [CI], 1.608-30.342, 3.49; 95% CI, 1.328-9.186, respectively). On comparing patients who expressed S100A4 or p53 with those who expressed neither, relapse rates were 58% vs. 25% in stage III (p = 0.011) and 95% vs. 59% in stage IV (M0) (p = 0.003). Conclusion: In addition to staging system, the expressions of S100A4 and p53 were significant predictive factors of relapse in gastric cancer after curative resection and adjuvant chemotherapy.     

Knockdown of S100A4 decreases tumorigenesis and metastasis in osteosarcoma cells by repression of matrix metalloproteinase-9

Osteosarcoma (OS), the most frequent bone tumor in children and adolescents, is highly malignant. Metastases are the major cause of death, and patients with relapse have a poor prognosis. Given the associations of S100A4 with OS and tumor metastasis, we explored its potential roles in OS metastasis. Among 32 OS (16 metastatic and 16 non- metastatic) specimens examined, we found a significant increase of S100A4 mRNA in metastatic tissues, and more importantly, expression of S100A4 and MMP-9 to be strongly correlated in patients who had lymph node or distant metastasis. We observed that siRNA mediated suppression of the S100A4 gene significantly reduced the proliferative and invasive capability of highly invasive OS cells, with a reduced rate of tumor growth and metastasis under in vivo conditions. Matrix metalloproteinase 9 (MMP-9) proved highly responsive to S100A4 gene suppression, demonstrating significant reduction in proteolytic activity, while overexpression of S100A4 increased the expression and proteolytic activity of MMP-9. Links of S100A4 with cell motility were confirmed by depletion which resulted in reduced cell migration. Moreover, loss of cell metastatic potential was completely rescued by overexpression of MMP-9. Collectively, our findings indicate that S100A4 contributes to OS metastasis by stimulating MMP-9 expression, suggesting potential as a novel diagnostic biomarker for OS progression as well as a therapeutic target.     

卡铂耐药蛋白S100A4在上皮性卵巢癌中的表达及与化疗耐药的关系

目的:检测S100A4蛋白在上皮性卵巢癌中的表达及其与化疗耐药的关系。方法:选择81例卵巢上皮性癌组织,分为耐药组40例,敏感组41例,应用免疫组织化学法检测S100A4在卵巢上皮性癌组织中的表达情况;MTT法测定卡铂对细胞的半数抑制浓度（IC50）,采用Western Blot检测卡铂化疗敏感的卵巢癌细胞株SKOV3及卡铂化疗耐药的卵巢癌细胞株SKOV3/CB中S100A4的表达情况。结果:S100A4分别在卵巢癌组织和卵巢癌细胞耐药组中的表达高于敏感组,与卵巢癌的化疗耐药有关（P<0.05）。S100A4在胞浆/胞核或胞核表达耐药组中高于敏感组,有统计学意义。卡铂对SKOV3组和SKOV3/CB组的IC50分别为28.83μmol/L和69.11μmol/L,因此SKOV3/CB对卡铂的耐药指数(RI)为2.4。结论:S100A4的表达与上皮性卵巢癌的化疗耐药密切相关,为卵巢癌患者个体化治疗提供依据。     

非小细胞肺癌患者血清中 S100 A4和 S100 A6表达及其临床意义

目的：探讨S100A4和S100A6在非小细胞肺癌患者血清中的表达及其临床意义。方法筛选非小细胞肺癌患者共36例,同期纳入健康体检者50例为对照组。采取酶联免疫吸附试验（ ELISA）法测定2组血清S100A4和S100A6水平;比较2组血清S100A4和S100A6水平,分析血清S100A4和S100A6水平与患者临床特征的相关性。2组随访2年,比较死亡患者与存活患者的血清S100A4和S100A6水平。结果与对照组比较,非小细胞肺癌组患者血清中S100A4和S100A6水平明显升高（P＜0．01）。血清S100A4和S100A6水平与非小细胞肺癌患者的年龄、性别及病理类型无相关性（P＞0．05）,而与肺癌患者的分化程度、TNM分期及淋巴结转移有显著性相关（P＜0．01）。随访2年共有10例患者死亡,26例存活;死亡患者入院时血清S100A4和S100A6水平明显高于存活组（P＜0．01）。结论非小细胞肺癌患者血清S100A4和S100A6水平明显升高,对非小细胞肺癌的诊断和预后判断具有一定临床价值。     

Metastasis promoter S100A4 is a potentially valuable molecular target for cancer therapy

The growth, invasion and metastatic spread of cancer have been identified with the deregulation of cell proliferation, altered intercellular and cell-substratum adhesion and enhanced motility and the deposition of disseminated cancer cells at distant sites. The identification of therapeutic targets for cancer is crucial to human welfare. Drug development, molecular modelling and design of effective drugs greatly depend upon the identification of suitable therapeutic targets. Several genetic determinants relating to proliferation and growth, invasion and metastasis have been identified. S100A4 appears to be able to activate and integrate pathways to generate the phenotypic responses that are characteristic of cancer. S100A4 signalling can focus on factors associated with normal and aberrant proliferation, apoptosis and growth, and differentiation. It is able to activate signalling pathways leading to the remodelling of the cell membrane and the extracellular matrix; modulation of cytoskeletal dynamics, acquisition of invasiveness and induction of angiogenesis. Therefore S100A4 is arguably a molecular target of considerable potential possessing a wide ranging biological activity that can alter and regulate the major phenotypic features of cancer. The evolution of an appropriate strategy that permits the identification of therapeutic targets most likely to be effective in the disease process without unduly affecting normal biological processes and function is an incontrovertible imperative. By virtue of its ability to activate interacting and multi-functional signalling systems, S100A4 appears to offer suitable targets for developing new therapeutic procedures. Some effectors of the S100A4-activated pathways might also lend themselves as foci of therapeutic interest.     

S100A4蛋白在肝癌组织中的表达及临床意义

目的:探讨SIOOA4蛋白在肝细胞癌、肝硬化、癌旁组织及正常肝组织中的表达及临床意义.方法:用组织芯片技术结合免疫组织化学法检测S100A4蛋白在肝癌相关组织中的表达差异,采用统计学方法分析其表达差异的临床意义.结果:免疫组织化学检测发现,S100A4蛋白在人原发性肝细胞癌、硬化肝组织、癌旁肝组织中表达较高,在正常肝组织中表达则很低,表达阳性率分别为70.2%、54.4%、41.7%和0.0%;统计学分析结果表明,S100A4蛋白表达影响肝癌患者的术后生存期,低表达患者的生存期比高表达患者延长.结论:S100A4蛋白在肝癌及相关组织中的表达率依次为,肝细胞癌＞癌旁肝＞肝硬化＞正常肝,在非微血管侵袭肝癌患者中S100A4阳性表达可明显降低其术后生存率.     

S100A7和S100A4在外阴鳞癌与外阴硬化性苔藓中的表达及意义

目的:检测外阴鳞癌（vulvar squamous cell carcinoma,VSCC）及外阴硬化性苔藓（vulvar lichen sclerosus,VLS）中S100A7和S100A4蛋白的表达,探讨其与疾病的发生发展关系。方法:采用免疫组化方法测定S100A7及S100A4蛋白在25例VSCC、20例VLS及15例外阴正常皮肤组织中的表达,并结合临床病理资料进行分析。结果:S100A7蛋白在VLS和VSCC中的表达明显高于正常皮肤（P＜0.05）,且早期VLS中的表达高于进展期（P＜0.05）;Ⅲ期VSCC中的表达高于Ⅰ-Ⅱ期（P＜0.05）,高分化VSCC中的表达高于中低分化（P＜0.05）。S100A4蛋白在VLS中的表达与正常皮肤无明显差异（P＞0.05）,但早期VLS中的表达高于进展期（P＜0.05）;S100A4在VSCC的癌巢中几乎不表达,但在间质细胞中的表达高于正常皮肤（P＜0.05）,中低分化VSCC中的表达高于高分化（P＜0.05）。S100A4表达与临床分期无关。结论:S100A7和S100A4蛋白高表达与VSCC的发生、发展有关,与VLS的进展呈负相关。     

S100A4蛋白在非小细胞肺癌中的表达与侵袭和转移的关系

背景与目的:实验证明S100A4在多种恶性肿瘤细胞中高表达,它可能在恶性肿瘤细胞的侵袭和转移等过程中发挥重要作用。本研究探讨S100A4在人非小细胞肺癌中的表达及其与侵袭和转移的关系。方法:采用免疫组化SP法检测41例非小细胞肺癌及6例正常肺组织中S100A4蛋白的表达水平。结果:S100A4在非小细胞肺癌中的阳性率(70.7%)显著高于正常肺组织(16.7%)(P<0.05);在肺腺癌中的阳性率(90.0%)明显高于肺鳞癌(52.4%)(P<0.01)。在TNM分期中,S100A4在Ⅲ Ⅳ期、Ⅱ期和Ⅰ期的阳性率分别为100.0%、66.7%和30.0%,Ⅲ Ⅳ期明显高于Ⅱ期和Ⅰ期(P<0.01),但是Ⅱ期和Ⅰ期间无显著性差异(P>0.05)。S100A4的阳性率在有淋巴结转移的非小细胞肺癌中(90.0%)明显高于无淋巴结转移组(52.4%)(P<0.01),且S100A4的表达与淋巴结转移密切相关(r=0.480,P=0.001)。肿瘤体积增大(<3cm,≥3cm),S100A4的阳性率明显升高(44.4%,91.3%)(P<0.001),且相关性显著(r=0.288,P=0.017)。S100A4的阳性率与非小细胞肺癌的病理分级无明显相关性(P>0.05)。结论:S100A4在非小细胞肺癌中的表达上调,且与淋巴结转移、TNM分期和肿瘤大小密切相关,提示S100A4与非小细胞肺癌的侵袭和转移有关。     

Sl00A4和E-cadherin表达与口腔鳞状细胞癌转移和预后的关系

目的:探讨S100A4和E-cadherin的表达量与口腔鳞状细胞癌(SCC)的临床病理学参数及SCC患者预后之间的关系.方法:采用免疫组织化学SABC法检测86例口腔鳞状细胞癌组织标本中的S100A4和E-cadherin表达,分析S100A4和E-cadherin在口腔SCC中表达的相关性,两者与临床病理指标及预后的关系.结果:S100A4在口腔SCC组织中的表达与肿瘤的淋巴结转移(P=0.001),肿瘤分级(P=0.009),肿瘤的浸润方式(P=0.015),分化程度(P=0.483)和生存率(P=0.014)具有相关性.E-cadherin表达与肿瘤的分级(P=0.005),浸润方式(P=0.037),淋巴结转移(P=0.005)及生存率(P=0.015)密切相关,且与S100A4表达成显著负相关(P=0.02).表现为S100A4(2+,3+)/E-cadherin(-,+)的患者淋巴结转移率最高(P=0.039),预后最差(P=0.002).结论:S100A4和E-eadherin均是预测口腔SCC转移趋势和预后的有价值的指标.     

S100钙结合蛋白A4在胃癌组织中的表达及意义

背景与目的：本研究探讨S100钙结合蛋白A4(S100 calcium-binding protein A4,S100A4)在胃癌旁正常组织、慢性胃炎、肠上皮化生、腺瘤样异型增生和胃癌的组织标本中的表达及与胃癌临床病理特征及预后的关系。方法：利用HE染色对所取胃组织标本进行病理组织学诊断;采用免疫组织化学方法检测标本S100A4蛋白的表达;实时定量聚合酶链反应(quantitative real-time pdymerase chain reaction,qRT-PCR)法检测S100A4 mRNA表达;蛋白[质]印迹法(Western blot)检测S100A4蛋白的表达;采用Kaplan-Meier分析累积生存率。结果：S100A4蛋白和mRNA的表达按以下顺序逐渐增加：胃癌旁正常组织<慢性胃炎<肠上皮化生<腺瘤样异型增生<胃癌。S100A4表达水平与肿瘤大小、浸润深度、淋巴管浸润、淋巴结转移和肿瘤TNM分期有关,但与患者的年龄和性别无关。在较大直径、较深浸润、淋巴结转移的胃癌和肠型癌中可发现S100A4基因的过表达。采用Kaplan-Meier单因素分析显示,弱或中度S100A4基因表达的患者与不表达的患者相比有较低的累积生存率。结论：在胃癌旁正常组织-慢性胃炎-肠上皮化生-腺瘤样异型增生-胃癌过程中,S100A4 mRNA和蛋白表达逐渐增高;S100A4表达与胃癌肿瘤大小、侵袭深度、淋巴结转移和不良预后呈正相关;S100A4过表达参与胃癌发生和演进过程,可以作为反映胃癌恶性程度的生物学指标。     

S100A4蛋白在宫颈鳞癌中的表达及意义

目的　研究S10 0A4蛋白在宫颈鳞癌组织中的表达及其临床意义。方法　应用免疫组织化学SP法检测 65例宫颈鳞癌组织和10例正常宫颈组织中S10 0A4蛋白。结果　在正常宫颈组织中S10 0A4蛋白不表达 ;在宫颈鳞癌组织中S10 0A4蛋白的表达率为3 5 .4% ( 2 3 /65 ) ;与正常宫颈组织比较 ,差异具有显著性 (P <0 .0 1)。S10 0A4蛋白在宫颈鳞癌中的表达与临床分期和淋巴结转移有关 (P <0 .0 1) ,与组织学分级无关 (P >0 .0 5 ) ;阳性细胞在血管平滑肌细胞以及淋巴细胞中亦有表达。结论　S10 0A4蛋白和宫颈鳞癌的侵袭和转移密切相关 ;S10 0A4蛋白可作为判定宫颈鳞癌临床病理特征的重要指标     

S100A4蛋白在乳腺癌组织的表达及临床意义

目的：探讨S100A4蛋白在乳腺癌组织的表达、相关性及临床意义。方法：采用免疫组织化学SP法检测55例乳腺癌组织和16例乳腺良性病变中S100A4蛋白的表达。结果：S100A4在乳腺癌组织中阳性率55．45％显著高于良性病变组织（P〈0．05），S100A4在腋淋巴结阳性组和复发／远处转移组的阳性表达率明显高于腋淋巴结阴性组和无复发、转移组（P〈0．05）；生存期≥5年组S100A4阳性率明显低于生存期〈5年组（P〈0．05）；与生存期呈负相关。S100A4蛋白与乳腺癌患者年龄、肿块大小、病理学分类、临床分期、ER、PR表达状态及月经状况无关（P〉0．05）。结论：乳腺癌组织S100A4蛋白表达增高与肿瘤的发生发展及预后密切相关，是判断乳腺癌生物学行为、预测转移趋势的有价值的参考指标，并有可能成为乳腺癌基因治疗的新靶点。     

S100A4调节MMP-13表达对甲状腺癌细胞侵袭能力的影响

目的探讨靶向S100A4对甲状腺癌细胞侵袭和转移的影响。方法以甲状腺癌BCPAP细胞或暴露于MMP-13抗体24h后的BCPAP细胞为研究对象,将S100A4基因小干扰RNA(siRNA)或S100A4/cDNA通过脂质体转染法转染BCPAP细胞;48h后采用RT-PCR和蛋白质印迹法检测S100A4mRNA、MMP-13mRNA和蛋白水平;Transwell侵袭实验和划痕实验检测BCPAP细胞侵袭能力的改变。结果转染S100A4siRNA 48h后,siRNA组S100A4mRNA表达量为(0.25,0.12),阴性对照组(NC)为(1.19,0.41),空白对照(Blank)组为(1.22,0.38),差异有统计学意义,H=13.68,P<0.05;siRNA组S100A4蛋白表达量为(0.40,0.21),NC组为(0.88,0.29),Blank组为(0.91,0.36),差异有统计学意义,H=15.74,P<0.05;siRNA组MMP-13mRNA表达量为(0.23,0.13),NC组为(1.08,0.28),Blank组为(1.12,0.37),差异有统计学意义,H=14.92,P<0.05;siRNA组MMP-13蛋白表达量为(0.42,0.16),NC组为(1.03,0.35),Blank组为(1.07,0.41),差异有统计学意义,H=17.64,P<0.05。质粒瞬时转染48h后,S100A4cDNA组S100A4蛋白表达量为(0.96,0.34),pCMV2-Myc组为(0.35,0.19),Blank组(0.37,0.22),差异有统计学意义,H=19.76,P<0.05。S100A4cDNA组MMP-13蛋白表达量为(1.21,0.47),pCMV2-Myc组为(0.38,0.21),Blank组为(0.37,0.23),差异有统计学意义,H=21.53,P<0.05;anti-MMP-13组蛋白表达量为(0.25,0.14),与S100A4cDNA组相比差异有统计学意义,z=5.89,P<0.05。细胞转染siRNA 48h后,Blank组穿膜细胞数为(37.86,3.52),NC组为(38.59,4.74),siRNA组为(11.38,2.16),差异有统计学意义,H=16.28,P<0.05;Blank组划痕48h后宽度为(0.24,0.11)cm,NC组为(0.28,0.05)cm,siRNA组为(1.98,0.13)cm,差异有统计学意义,H=16.65,P<0.05。质粒瞬时转染细胞48h后,Blank组穿膜细胞数为(39.68,3.76),pCMV2-Myc组为(41.66,8.02),S100A4cDNA组为(70.14,7.85),差异有统计学意义,H=19.24,P<0.05;anti-MMP-13组为(43.56,7.86),与S100A4cDNA组相比差异有统计学意义,z=5.87,P<0.05;Blank组划痕48h后宽度为(0.31,0.11)cm,pCMV2-Myc组为(0.29,0.09)cm,S100A4cDNA组为0,差异有统计学意义,H=21.84,P<0.05;anti-MMP-13组为(1.96,0.17)cm,与S100A4cDNA组相比差异有统计学意义,z=12.03,P<0.05。结论S100A4通过调节MMP-13表达影响甲状腺癌细胞的侵袭能力,靶向S100A4可下调MMP-13表达抑制甲状腺癌的侵袭转移。     

Small interfering RNA-directed knockdown of S100A4 decreases proliferation and invasiveness of osteosarcoma cells

Osteosarcoma is the most common osteogenic malignant tumor characterized by a high level of malignancy, relapse, metastasis and poor prognosis. S100A4 has been implicated in the proliferation, cell cycle progression, and metastasis of many malignant tumors, although the roles of S100A4 in osteosarcoma have not been documented. This study showed that the expression of S100A4 was found in two osteosarcoma cell lines MG-63 and U-2OS, and in 70.7% of osteosarcoma clinical tissues, and the expression was correlated with the expression of CD44V6. In addition, transfection with S100A4 siRNA significantly reduced the proliferation and the invasiveness of MG-63 cells. Furthermore, S100A4 siRNA down-regulated the expression of CD44 and MMP2, suggesting that S100A4 may promote the proliferation, invasion and metastasis of osteosarcoma cells by regulating the expression of other proteins that are crucial in modulating cell–ECM adhesion and facilitating ECM degradation. Therefore, siRNA-directed knockdown of S100A4 may represent a viable clinical therapy for osteosarcoma.     

S100A4与p53在活细胞内相互作用研究

目的体外研究发现S100A4蛋白可与p53蛋白结合,但至今尚不清楚S100A4与p53蛋白能否在活细胞内发生相互作用。本研究旨在确定S100A4与p53在活细胞内的相互作用。方法采用光学生物传感器体外检测S100A4蛋白与p53蛋白的结合能力。应用激光共聚焦显微镜的荧光共振能量转移(fluorescence resonance energy transfer,FRET)技术检测Hela细胞(人宫颈癌细胞株)内S100A4与p53蛋白的相互作用。结果光学生物传感器体外检测发现,野生型S100A4蛋白与p53蛋白结合能力强,对照组突变型S100A4蛋白则失去与p53蛋白的结合能力。采用FRET技术发现,表达CFP-S100A4和p53-YFP融合蛋白的Hela细胞中,细胞核内p53-YFP的荧光强度衰减后,CFP-S100A4的荧光强度增强,发生FRET;而细胞质中没有发生FRET。作为对照,表达突变CFP-mS100A4-C和p53-YFP融合蛋白,或表达S100A4和YFP的Hela细胞内没有发生FRET,表明S100A4和p53之间的相互作用发生在活细胞的细胞核中。结论活细胞内S100A4可直接与细胞核中的p53相互作用,这可能是S100A4蛋白在体内发挥生物学作用的分子基础,提示阻断S100A4的钙结合位点可能是潜在的抗肿瘤转移作用靶点。     

AKT2 S100A4 及MMP-9 在鼻咽癌组织中的表达*

目的:探讨AKT 2、S100A4 及MMP-9 在鼻咽癌组织中的表达、相互关系及临床意义。方法:应用免疫组化EliVision 二步法检测50例鼻咽癌组织、25例慢性鼻咽炎组织标本中AKT 2、S100A4 及MMP-9 蛋白的表达,并分析三者与鼻咽癌患者临床特征的关系及三者表达的相关性。结果:鼻咽癌组织中AKT 2、S100A4 及MMP-9 的阳性表达率分别为48.0%（24/50）、52.0%（26/50）、74.0%（37/50）,显著高于慢性鼻咽炎组织的8.0%（2/25）、0（0/25）、36.0%（9/25）,P 均<0.01;AKT 2 和S100A4 的表达均与鼻咽癌颈淋巴结转移及临床分期相关（P 均<0.05）,MMP-9 的表达与鼻咽癌颈淋巴结转移相关（P<0.05）,而三者的表达与患者性别、年龄及T 分期无关（P 均>0.05）;鼻咽癌组织中AKT 2 和S100A4 与MMP-9 的表达呈正相关（P 均<0.01）,AKT 2 与S100A4 的表达无关（P>0.05）。 结论:AKT 2、S100A4 及MMP-9 的高表达在鼻咽癌的发生、发展及转移方面可具有重要作用,AKT 2 和S100A4 可能通过上调MMP-9 的表达而促进鼻咽癌的发展及转移,联合检测三者的表达情况对判断鼻咽癌生物学行为和预测肿瘤转移有一定的临床价值。