乳腺癌钼靶X线显示钙化灶与ER、PR和c-erbB-2表达的相关性研究

目的:探讨乳腺癌钼靶X线钙化与ER、PR及c-erbB-2表达的相关性及其临床意义.方法:分析86例乳腺癌钼靶X线片,将其分为有钙化组(46例)和无钙化组(40例);将切除的肿瘤标本行HE及免疫组织化学染色,检测并比较两组ER、PR和c-erbB-2的表达率.结果:乳腺癌钼靶X线有钙化组ER和PR的表达率均略高于无钙化组(56.5% vs 55.0%,45.6% vs 42.5% ),但差异无统计学意义 (P＞0. 05);有钙化组c-erbB-2表达率高于无钙化组(65.2% vs 40.0%),差异有统计学意义(P＜0. 05).结论:乳腺癌钼靶X线钙化与ER、PR表达无相关性,但与c-erbB-2表达密切相关;钼靶X线钙化可以粗略反映c-erbB-2表达情况,可为乳腺癌治疗策略的制定和预测预后提供参考.     

Artemin在三阴性乳腺癌中的表达及其临床意义

目的 初步分析和探讨三阴性乳腺癌患者artemin表达情况,及其对疾病预后的价值.方法 选取我院肿瘤科2005年7月至2009年7月收治的149例浸润性乳腺癌患者为研究对象,根据ER、PR和HER-2免疫组化检测结果,将其分成三阴性乳腺癌组和非三阴性乳腺癌组,采用RT-PCR和免疫组织化学方法检测artemin在两组患者肿瘤组织中的表达情况,并分析artemin在不同组织学分级、临床分期和N分期三阴乳腺癌组患者中表达情况.结果 三阴性乳腺癌组免疫组化artemin阳性表达率为79.22％ (61/77),高于非三阴性乳腺癌组患者25.00％ (18/72),差异有统计学意义(x2=5.170,P =0.006);三阴性乳腺癌组artemin mRNA表达量为(3.36±0.04)×103 copies/mL,非三阴性乳腺癌组患者为(2.52±0.06)×103copies/mL,两组差异有统计学意义(x2=3.416,P=0.04);三阴性乳腺癌患者中artemin表达率与组织学分级、临床分期和N分期相关,差异具有统计学意义(P＜0.05),而与就诊年龄、恶性肿瘤家族史、肿瘤长径以及绝经状态无关(P＞0.05).结论 三阴性乳腺癌患者的artemin表达率显著高于非三阴性乳腺癌患者,artemin在三阴性乳腺癌组织中的表达与组织学分级、临床分期和N分期密切相关,临床检测artemin可以对患者疾病的发展和预后判断提供重要的依据.     

PLK1在乳腺癌分子亚型中的表达及其与基底细胞样型乳腺癌的关系

目的:探讨乳腺癌各分子亚型中PLK1的表达及其与基底细胞样型乳腺癌的关系.方法:回顾性分析803例乳腺浸润性导管癌的临床病理资料,按照Nielsen标准将乳腺浸润性导管癌分成腺腔A型、腺腔B型、HER-2过表达型、基底细胞样型和普通乳腺样型.检测PLK1在5种不同乳腺癌亚型中的表达水平并分析其与基底细胞样型乳腺癌的关系.结果:PLK1在基底细胞样型、普通乳腺样型、HER-2过表达型、腺腔A型及腺腔B型乳腺癌中的阳性表达率分别为58.94%(56/95),39.39%(65/165),33.33%(22/66),17.91%(79/441)及5.56%(2/36).PLK1在ER阴性的乳腺癌分子亚型中的表达显著高于其在ER阳性的乳腺癌分子亚型中的表达,差异具有统计学意义(P<0.05);PLK1的表达与ER呈负相关,与Ki-67表达呈正相关(P<0.01),与HER-2无显著相关性.ER阴性乳腺癌中,PLK1在基底细胞样型乳腺癌中的阳性表达率最高,显著高于其在HER-2过表达型及普通乳腺样型乳腺癌中的表达,差异有统计学意义(P<0.05).而HER-2过表达型与普通乳腺样型中相比,PLK1的表达差异无统计学意义(P=0.390).PLK1的表达与基底细胞样型乳腺癌的淋巴结转移及临床分期相关,而与肿瘤大小及患者年龄无关.结论:PLK1过表达可能与ER阴性的基底细胞样型乳腺癌关系更密切,并在基底细胞样型乳腺的浸润、转移中起重要作用.     

CK5/6、EGFR和E-cadhenrin在三阴性乳腺癌中的表达及意义

目的探讨CK5/6、E-cadhenrin及EGFR在三阴性乳腺癌中的表达与主要临床病理参数及预后的关系。方法收集浸润性乳腺癌278例,其中三阴性乳腺癌62例(22.30%),非三阴性乳腺癌216例(77.70%)。通过免疫组织化学方法检测CK5/6、E-cadhenrin及EGFR在乳腺癌中的表达,并分析三阴性乳腺癌中CK5/6、E-cad及EGFR与患者临床病理学参数和预后的关系。结果 CK5/6和EGFR在三阴性乳腺癌中的阳性表达率明显高于非三阴性乳腺癌(P0.05),而E-cadhenrin在三阴性乳腺癌的阳性表达率明显低于非三阴性乳腺癌(P0.05)。CK5/6与EGFR的表达呈明显的正相关(r=0.417,P0.05),二者与E-cadhenrin均呈明显的负相关(r=7.59,P0.05;r=0.333,P0.05)。三阴性乳腺癌中CK5/6和EGFR的表达与淋巴结转移、临床分期及组织学分级密切相关(P0.05),E-cad-herin的表达与患者淋巴结转移和临床分期密切相关(P0.05),与其他临床参数无关(P0.05)。Kaplan-Meier生存分析显示三阴性乳腺癌中CK5/6的阳性表达及E-cadherin的阴性表达的患者生存时间明显短于CK5/6阴性及E-cadherin阳性的患者(P0.05)。结论 CK5/6和EGFR在三阴性乳腺癌中高表达,E-cadhenrin在三阴性乳腺癌中低表达,CK5/6的阳性表达及E-cadherin的阴性表达与三阴性乳腺癌患者不良预后密切相关。     

乳腺癌中高迁移率族蛋白B1蛋白表达及其临床病理意义

目的探讨高迁移率族蛋白B1(HMGB1)蛋白在乳腺癌中的表达及临床病理意义。方法收集2006—2018年浙江省东阳市人民医院病理科浸润性乳腺癌石蜡标本417例和同时切除的正常乳腺组织石蜡标本26例。采用免疫组织化学EnVision法检测和比较浸润性乳腺癌组织和正常乳腺组织中HMGB1蛋白的表达。分析HMGB1蛋白胞核高表达及胞质阳性表达与乳腺癌患者临床病理特征的关系。结果(1)乳腺癌中HMGB1蛋白胞核高表达率及胞质阳性率分别为80.8%(337/417)和16.8%(70/417),而其在正常乳腺组织中分别为46.2%(12/26)和0。乳腺癌中HMGB1蛋白胞核高表达率和胞质阳性率均明显高于正常乳腺组织(分别P<0.001,P=0.046)。(2)组织学级别高、雌激素受体(ER)阴性、孕激素受体(PR)阴性的乳腺癌患者,其HMGB1蛋白胞核高表达率明显更高(分别P=0.006,P=0.004,P<0.001),胞质阳性率也明显更高(均P<0.001)。Logistic回归模型多因素分析显示乳腺癌患者HMGB1蛋白胞核高表达的独立相关因素为肿瘤组织学分级(OR=2.188,95%CI=1.078~4.443,P=0.030),而HMGB1蛋白胞质阳性表达的独立相关因素包括肿瘤组织学分级(OR=3.031,95%CI=1.600~5.742,P=0.001)、ER(OR=0.129,95%CI=0.034~0.494,P=0.003)及TNM分期(OR=3.820,95%CI=1.042~14.001,P=0.043)。(3)Cox比例风险模型多因素分析显示HMGB1蛋白胞核高表达是影响乳腺癌患者总生存的独立危险因素(HR=0.366,95%CI=0.138~0.972,P=0.044)。结论HMGB1蛋白胞核高表达及胞质阳性表达与乳腺癌患者多项预后不良因素密切相关,有望成为抗乳腺癌治疗的一个潜在生物学标志。     

甲状腺乳头状癌组织中FOXQ1和CDK4的表达与临床病理特征及预后的相关性研究

目的 探讨甲状腺乳头状癌( PTC) 组织中 FOXQ1 和 CDK4 的表达与患者临床病理特征及预后的关系。方法 选择进行手术切除的 110 例 PTC 患者的癌组织及癌旁组织,采用免疫组化染色法检测 PTC 组织及癌旁组织中 FOXQ1 和 CDK4 蛋白表达,分析 FOXQ1 和 CDK4 的表达与患者临床病理特征及预后的关系。PTC 组织中 FOXQ1 与 CDK4 蛋白表达的相关性分析采用Spearman 秩相关检验。结果 PTC 组织中 FOXQ1 蛋白的阳性表达率为 64. 5% ( 71 /110) ,高于癌旁组织中 FOXQ1 蛋白的阳性表达率 33. 6% ( 37 /110) ,差异有统计学意义( χ²= 21. 025,P = 0. 000) 。PTC 组织中 CDK4 蛋白的阳性表达率为 54. 5% ( 60 /110) ,高于癌旁组织中 CDK4 蛋白的阳性表达率 7. 3% ( 8 /110) ,差异有统计学意义( χ²= 57. 554,P = 0. 000) 。FOXQ1 和 CDK4 蛋白在 PTC 组织...     

蛋白激酶B在乙型肝炎病毒感染原发性肝细胞癌组织中的表达及临床意义

目的:探讨蛋白激酶B(PKB/Akt)在乙型肝炎病毒(HBV)感染原发性肝细胞癌组织中的表达及及临床价值.方法:采用SP免疫组化法,检测35例HBV感染原发性肝细胞癌(HBV肝癌)、乙肝后肝硬化和正常肝组织中PKB/Akt的表达.结果:HBV肝癌组和肝硬化组PKB阳性表达率分别为94.3%和66.7%,显著高于对照组(40.0%),有统计学差异(P<0.05);HBV肝癌组阳性表达率显著高于肝硬化组(P<0.05);肿瘤浸润和淋巴结转移组织中PKB/Akt阳性表达率显著高于无肿瘤浸润和淋巴结转移组织(P<0.05),PKB/Akt阳性表达率在性别、年龄、肿瘤大小和肿瘤分化程度等病理因素之间比较差异无统计学意义(P>0.05).结论:PKB/Akt在HBV肝癌组织中呈高表达,PKB/Akt在HBV肝癌的肿瘤浸润、淋巴结转移的机制中起着重要的作用.     

hRad17在浸润性乳腺癌中表达及其与细胞增殖、凋亡的关系

目的 探讨乳腺癌组织中hRad17表达及其与细胞增殖、凋亡之间的关系.方法 采用免疫组化SP法检测90例乳腺浸润性癌、8例乳腺原位癌及20例乳腺良性病变组织中hRad17表达.测定90例乳腺浸润性癌组织中Ki-67、微小染色体维持蛋白7(minichromosome maintenance proteins,MCM7)、Bcl-2、p53、ER、PR、c-erbB-2的表达.结果 hRad17蛋白在乳腺浸润性癌、乳腺原位癌和乳腺良性病变三组病例中表达差异有统计学意义(P<0.05).90例乳腺浸润性癌中,hRad17阳性表达56例(62.2%).乳腺浸润性癌的hRad17的阳性表达与乳腺癌的临床分期、组织学分级、淋巴结转移及Ki-67、MCM7、Bcl-2表达密切相关,与患者生存期呈负相关(P<0.05).hRad17的表达与患者年龄、肿块大小、组织学类型和p53、ER、PR、c-erbB-2表达均无关(P>0.05).结论 hRad17在乳腺癌中表达上调,提示在乳腺癌发生、发展中起重要作用.hRad17可成为判断乳腺癌预后新的分子标记物.     

非小细胞肺癌中CIP2A的表达及与临床病理的相关性

目的 探讨蛋白磷酸酶2A的癌性抑制因子(cancerous inhibitor of protein phosphatase 2A,CIP2A)在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的表达及其与临床病理因素的相关性.方法 采用免疫组化SP法检测92例肺癌组织及10例正常肺组织中CIP2A与c-Myc蛋白表达及相关性,干扰CIP2A的表达并检测其对细胞增殖的影响.结果 在NSCLC组织中,CIP2A的表达定位于细胞质与细胞核中,以胞质表达为主.CIP2A阳性率为70.65%(65/92),高于正常肺组织(P＜0.05).c-Myc在CIP2A阴性的肿瘤中阴性率为77.78%(21/27),阳性率为22.22%(6/27);c-Myc在CIP2A阳性的肿瘤中阳性率为76.92%(50/65),阴性率为23.08%(15/65).CIP2A、c-Myc的表达与患者不良预后相关,CIP2A阳性与患者年龄、性别、肺癌类型、TNM分期、淋巴结转移均无相关性.转染CIP2A特异性siRNA于A549和H1299肺癌细胞系中,发现CIP2A表达下降的同时,c-Myc蛋白水平明显下调,细胞增殖能力明显下降(P＜0.05),集落数目明显减少(P＜0.05).结论 CIP2A在肺癌中过表达,且与c-Myc表达及患者预后明显相关,干扰CIP2A可下调c-Myc表达并抑制肺癌细胞增殖.     

埃兹蛋白在乳腺癌中的表达及其临床意义

目的 通过检测埃兹蛋白在浸润性乳腺癌、乳腺导管内癌及正常乳腺组织中的表达,探究埃兹蛋白在乳腺癌组织中的表达的临床意义。方法 随机选取南昌大学第一附属医院40例浸润性乳腺癌患者及32例乳腺导管内癌患者,另外选择同期来我院健康体检者22例。通过免疫组化链霉亲和素-过氧化物酶法（S-P）法分别检测埃兹蛋白在22例正常乳腺组织、32例乳腺导管内癌组织和40例浸润性乳腺癌组织中的表达,参照病理结果进行分析。结果 埃兹蛋白在40例浸润性乳腺癌的阳性表达率为72.50%、在32例乳腺导管内癌的阳性表达率为40.63%、在正常乳腺组织中的阳性表达率13.64%,浸润性乳腺癌中埃兹蛋白的表达高于其他两种组织,差异具有统计学意义（P＜0.05）;埃兹蛋白在G3期乳腺癌组织中的表达高于在G1~G2期乳腺癌组织中的表达,差异具有统计学意义（P＜0.05）;埃兹蛋白在淋巴结转移患者中的阳性表达率高于在无淋巴结转移的患者中的阳性表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在＜40岁的患者中的阳性表达率低于在年龄≥40岁的患者中的表达率,差异统计学意义显著（P＜0.01）;埃兹蛋白在PR阳性患者中的阳性表达率低于在PR阴性患者中的表达率,差异具有统计学意义（P＜0.05）;乳腺癌患者中埃兹蛋白的表达与组织学分级、腋窝淋巴结转移及年龄呈正相关（P＜0.05）,与PR呈负相关（P＜0.05）;埃兹蛋白在浸润性润腺癌中的表达与乳腺癌临床分期、脉管侵犯、肿瘤大小、患者月经状态以及Her-2、ER、Ki-67的表达无相关性（P＞0.05）。结论 埃兹蛋白在乳腺癌和正常乳腺组织中的表达不同,对判断乳腺肿瘤性质具有重要参考意义;此外,埃兹蛋白能够帮助判断乳腺癌的转移潜能和预后,可能启发乳腺癌新的靶向治疗。     

Akt/PKB activation in gastric carcinomas correlates with clinicopathologic variables and prognosis

Akt/protein kinase B (PKB) plays an important role in cell survival. However, the role of Akt in the biology of gastric cancer has not been well studied. We sought to investigate the expression of Akt or phosphorylated Akt (pAkt) in human gastric carcinomas and to analyze the relationship between Akt or pAkt and the clinicopathologic parameters. The expressions of Akt and pAkt were evaluated immunohistochemically in 311 gastric carcinomas using the tissue array method. Akt expression was detected in 74% of the tumors and pAkt expression in 78%. pAkt was highly expressed in the early stage of pTNM (p=0.011). We also found an inverse association between pAkt and lymphatic invasion (p=0.01) or lymph node metastasis (p=0.008). pAkt expression was significantly correlated with a higher survival in patients with stage I carcinomas (p=0.0003). Interestingly, combined evaluation revealed that the group with pAkt-positive and lymph node-negative carcinomas showed a better prognosis than the other groups (p<0.0001). In addition, pAkt was shown to correlate positively with APC (p=0.002) and Smad4 (p<0.0001) expression. These findings suggest that pAkt expression may help to predict the clinical outcome of gastric cancer patients.     

Proximity ligation assays for isoform-specific Akt activation in breast cancer identify activated Akt1 as a driver of progression

The PI3K/Akt signal transduction pathway plays an important role in cancer progression and cell survival. Akt activation is associated with poor outcome in endocrine-treated breast cancer, whereas high levels of cytoplasmic Akt2 are associated with an improved overall survival. Proximity ligation assays (PLAs) were used to determine quantitative expression levels of isoform-specific activation (phosphorylation) of Akt1 and Akt2 in formalin-fixed, paraffin-embedded cell lines and breast cancer tumour tissues in situ. PLAs demonstrated a range of expression in breast cancer samples for total pAkt1 and pAkt2. High levels of pAkt1 were associated with reduced DRFS (HR: 1.45, 95% CI 1.14-1.83, p = 0.002) and OS (HR: 1.42, 95% CI 1.10-1.83, p = 0.007). When PLA results were combined, patients that had high levels of pAkt1 only had a significantly decreased DRFS (HR: 1.92, 95% CI 1.34-2.76, p = 0.005) and OS (HR: 1.94, 95% CI 1.32-2.86, p = 0.008) compared to other patients. Using PLAs to discriminate activation of Akt1 versus Akt2 suggests that Akt1 drives progression in early breast cancers. In cases where both Akt1/Akt2 are activated, Akt2 may act to reverse this effect. Using PLAs, we have measured activation of Akt1 and Akt2 proteins separately in situ in FFPE breast cancer samples.     

Prognostic relevance of activated Akt kinase in node-negative breast cancer: a clinicopathological study of 99 cases.

Patients with lymphnode-negative breast cancer show a 10-year tumor recurrence rate of approximately 30%. Therefore, it is important to identify high-risk patients who would benefit from further adjuvant therapy. For this purpose, we examined the activation state of two kinases important in the regulation of cell proliferation and apoptosis in a series of 99 node-negative breast cancer cases with a mean follow-up of 10 years: Akt and extracellular regulated kinase (ERK1/2). The activation of Akt and ERK1/2 was investigated by immunohistochemistry using phospho-specific antibodies. The results were correlated with HER-2/neu expression, histological grading, receptor status, overall survival (OS) as well as with cell proliferation (Ki67 immunoreactivity, mitotic count) and tumor apoptosis assessed by TUNEL staining. Activation of Akt (pAkt) but not activation of ERK1/2 (pERK1/2) correlated with HER-2/neu overexpression (P<0.05) and was related to reduced tumor apoptosis (P<0.05). No association was found between pAkt or pERK1/2 with cell proliferation assessed by Ki67 and mitotic count (MC). Survival analysis of receptor status, HER2/neu expression, histological grading, MC and pAkt immunoexpression showed a significant correlation with decreased OS, but only pAkt reached statistical significance in the multivariate Cox regression analysis (P=0.015). Activation of Akt in node-negative breast cancer may indicate aggressive tumor behavior and may constitute an independent prognostic factor of OS. The determination of pAkt status may be of value in identifying high-risk patients, who would benefit from adjuvant therapy, and gives a rationale to investigate new therapy strategies by specific inhibition of the Akt signaling pathway in breast cancer.     

PKIB expression strongly correlated with phosphorylated Akt expression in breast cancers and also with triple-negative breast cancer subtype

The cAMP-dependent protein kinase inhibitor-?? (PKIB) is presumed to be one of the regulatory factors controlling the cAMP-dependent protein kinase A signaling pathway. The aim of this study was to investigate the frequency and patterns of PKIB overexpression in human breast cancer. We also examined the relationship between PKIB and phosphorylated Akt (pAkt) expression in the tumors. Using immunohistochemical techniques, we examined the expression of PKIB, ER, PR, HER2, and pAkt in 148 primary human breast carcinomas. We then analyzed the relationships between PKIB expression and that of pAkt, ER, PR, and HER2, as well as between PKIB expression and various clinicopathological characteristics. We assessed 64 and 27 cases, respectively, as positive for either PKIB or pAkt expression; 20 cases were positive for both PKIB and pAkt. We observed a significant positive correlation between the expression of PKIB and that of pAkt (P = 0.006). We showed by immunohistochemical analyses that PKIB expression was positively correlated with triplenegative breast cancers (P = 0.0004). These findings provide evidence for PKIB overexpression associated with pAkt expression. Furthermore, PKIB expression was strongly correlated with triple-negative breast cancer, suggesting that PKIB expression might contribute to the tumor behavior and development of breast cancer.     

Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer

Introduction: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression.

Methods: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples.

Results: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition.

Discussion: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

     

Activation of Akt and the signaling of phosphorylated Akt in the L5 dorsal root ganglia in aging rats

Introduction

Protein kinase B (PKB)/Akt is a kinase that is responsive towards insulin-like growth factor (IGF-1) and nerve growth factor (NGF). Detected in the cytosol, Akt is activated by phosphorylation at Thr308/Ser473 residue. The phosphorylated Akt (pAkt) is translocated into the nucleus via the of phosphatidylinositide 3-kinases (PI3K)-Akt pathway. Contradicting results have been reported on the expression of Akt and pAkt in aged animals. The study is conducted to determine the effect of aging on the Akt and pAkt signaling in the L5 dorsal root ganglia (DRG).

溶质载体家族6成员1通过调节PI3K/Akt信号通路磷酸化促进乳腺癌细胞的迁移和侵袭

目的 探讨溶质载体家族6成员1（SLC6A1）对乳腺癌细胞迁移和侵袭的影响及分子机制。 方法 下载并综合分析数据集GSE125989和GSE100534,筛选差异基因;通过STRING数据库和Cytoscape 3.6.1 软件构建差异基因的蛋白相互作用网络,并筛选hub基因;通过Ualcan和GEPIA数据库检测hub基因SLC6A1在乳腺癌中的表达及其对预后的影响;转染SLC6A1-siRNA干扰乳腺癌细胞MDA-MB-231中SLC6A1的表达;细胞划痕实验和Transwell实验检测乳腺癌细胞迁移和侵袭能力的变化;基因集富集分析和Western blotting检测SLC6A1在乳腺癌中发挥作用的机制;采用SC79激活Akt通路并检测细胞迁移和侵袭能力的变化。 结果 共筛选出92个乳腺癌原位癌与转移瘤的差异基因,并确定Ⅰ型胶原蛋白α1（COL1A1）、血管内皮生长因子A（VEGFA）、SLC6A1等20个hub基因;SLC6A1在乳腺癌组织中高表达（P＜0.001）,且与患者预后相关（P=0.01）;SLC6A1表达被干扰后,乳腺癌细胞迁移和侵袭能力显著下降（P＜0.05）;SLC6A1表达降低可抑制PI3K/Akt信号通路的磷酸化（P＜0.05）;激活PI3K/Akt通路后 SLC6A1-siRNA对乳腺癌细胞迁移和侵袭的抑制作用消失（P＜0.05）。 结论 SLC6A1通过调节PI3K/Akt信号通路促进乳腺癌的侵袭和转移。     

High-level expression of fatty acid synthase in human prostate cancer tissues is linked to activation and nuclear localization of Akt/PKB

Many human epithelial cancers, particularly those with a poor prognosis, express high levels of fatty acid synthase (FAS), a key metabolic enzyme linked to the synthesis of membrane phospholipids in cancer cells. In view of the recent finding that in the human prostate cancer cell line LNCaP, overexpression of FAS can be largely attributed to constitutive activation of the phosphatidylinositol-3 (PI3) kinase/Akt kinase pathway, the activation status of the Akt pathway, and whether this activation coincides with increased FAS expression, was examined in clinical prostate cancer tissues. Using well-preserved frozen prostatic needle biopsies and a sensitive Envision detection technique, S473-phosphorylated Akt (pAkt) was found in 11/23 low-grade prostatic intraepithelial neoplasia (PIN) lesions, in all (36/36) high-grade PINs, and in all (86/86) invasive carcinomas. Non-neoplastic tissues were negative. Interestingly, in low-grade PINs and low-grade carcinomas, pAkt was mainly cytoplasmic or membrane-bound and was associated with moderate elevation of FAS expression. In 24/36 high-grade PINs and 82/88 invasive carcinomas, pAkt was found at least partly in the nucleus. Greater nuclear pAkt staining, and higher FAS expression, correlated with a higher Gleason score. In the light of previous findings that pAkt plays a causative role in the overexpression of FAS in cancer cells in culture, these data strongly suggest that high-level expression of FAS in prostate cancer tissues is linked to phosphorylation and nuclear accumulation of Akt.     

Clinicopathological correlations of mTOR and pAkt expression in non-small cell lung cancer

The Akt/mammalian target of rapamycin (mTOR) pathway is up-regulated in many human cancers, and agents targeting the mTOR pathway are in various stages of clinical development and application. Expression of pAkt and mTOR was studied by immunohistochemical analysis of 574 surgically resected non-small cell lung cancer (NSCLC) specimens on a tissue microarray. The results were correlated with clinicopathological features. Expression of mTOR showed a strong correlation with the expression of pAkt (p?相似文献   

Activated Akt as an indicator of prognosis in gastric cancer

The immunohistochemical expression of phosphorylated (activated) Akt (pAkt) in 50 advanced gastric carcinomas has been analyzed and the results correlated with age, sex, location in the stomach, histotype, stage, survival, mitotic and apoptotic index, some cell cycle regulators (cyclin D1, cyclin E, p34/cdc2, p27/kip1), and cell proliferation. There was a statistically significant direct correlation between pAkt expression (both cytoplasmatic and nuclear) and depth of infiltration of the tumor, number of infiltrated lymph nodes and p34/cdc2 expression, and between prevalently nuclear pAkt and cyclin D1 and cyclin E. Conversely, there was a significant inverse correlation between nuclear pAkt and apoptotic index and between cytoplasmatic and nuclear pAkt and patient survival. No correlation was found between pAkt and sex, age, tumor location, histotype, mitotic index, and cell proliferation. These findings suggest that pAkt may be considered an indicator of tumor progression and patient survival in gastric cancer.