表皮生长因子和受体在子宫内膜发育及胚胎着床中的作用

表皮生长因子 (ＥＧＦ)早在 60年代由ＳｔａｎｌｅｙＣｏｈｅｎ[1] 在研究神经生长因子时首先发现。它是一种含 5 3个氨基酸的单链多肽类物质 ,人体多种组织 (上皮组织、中胚层组织 )均有分布 ,可参与多种生理、病理功能的调节。近年来 ,随着生殖医学的发展 ,ＥＧＦ在生殖过程中的作用日益受到人们的重视。本文通过对近几年的文献回顾 ,简要综述ＥＧＦ及ＥＧＦ -Ｒ在子宫内膜发育及诱导胚胎着床方面的作用。一、ＥＧＦ及ＥＧＦ -Ｒ概述人ＥＧＦ基因 (ｈＥＧＦ)位于 4号染色体的ｑ2 5 - ｑ2 7区 ,全长 12 0ｋｂ ,包括 2 4个外显子和 2 3个内…     

无雄激素条件下表皮生长因子诱导前列腺癌细胞系增殖及雄激素受体磷酸化

目的探讨在无雄激素的条件下,表皮生长因子对前列腺癌细胞增殖及雄激素受体磷酸化的影响。方法以LNCaP及LAPC4 AR为研究对象,在无雄激素的条件下,EGF处理后,Western blot方法测定LNCaP及LAPC4 AR磷酸化状态;siRNA转染方法敲除Src基因或Ack1基因,观察对AR磷酸化的影响;CCK-8检测细胞增殖;定时定量RT-PCR检测前列腺特异抗原及人体激肽释放酶2 mRNA表达。结果 EGF通过Src激酶和另一未知激酶导致AR Tyr-534及AR Tyr-267特异位点磷酸化;相比未用EGF对照组,EGF能够促进前列腺癌细胞增殖(P0.05),增加前列腺特异抗原(P0.05)及人体激肽释放酶2 mRNA表达(P0.05)。结论 EGF通过细胞内非受体酪氨酸激酶使AR特异位点磷酸化,诱导前列腺癌细胞增殖。     

Cyr61蛋白在子宫内膜腺癌中的表达及意义

目的： 探讨富含半胱氨酸61（Cyr61）在子宫内膜腺癌中的表达及意义。 方法： 应用免疫组化技术检测65例子宫内膜腺癌、15例子宫内膜增生过长,正常子宫内膜增殖期及分泌期各30例组织中Cyr61、雌激素受体（ER）、孕激素受体（PR）及细胞核增殖相关抗原（Ki67）的表达,分析Cyr61的表达与子宫内膜癌临床病理特征的关系。 结果： （1）60例（60/65,92.3％）子宫内膜腺癌Cyr61表达阳性,高于正常子宫增殖期和分泌期内膜（P<0.05）。（2）ER、PR阴性病例子宫内膜癌组织Cyr61表达高于其阳性病例,Ki67阳性病例Cyr61表达升高（P<0.05）。（3）Cyr61表达与病理分级、淋巴细胞侵润、组织坏死有关（P<0.05）,而与年龄、临床分期和子宫肌层侵润深度,预后无关（P>0.05）。 结论： Cyr61可能与子宫内膜癌肿瘤细胞恶性潜能有关。     

表皮生长因子受体

表皮生长因子受体 (EGFR)是一种具有酪氨酸激酶活性的膜表面受体 ,其胞内区的 3个亚区是其发挥酪氨酸激酶活性、介导信号转导的关键部位。表皮生长因子受体和其他的 erb B受体可形成同源和异源的多种二聚体 ,不同的二聚体与表皮生长因子受体的 6种配体形成的不同组合可将不同的细胞外刺激传入胞内。表皮生长因子可激活多种下游信号路径 ,产生多种生物学效应 ,ras- raf- MEK- erk/ MAPK途径与增殖的激活有关 ,PI3K- PKC-IKK途径与细胞移动性的增强有关。表皮生长因子受体与肿瘤的发生发展和器官的修复有密切的关系 ,针对表皮生长因子受体的肿瘤治疗和器官修复具有良好的应用前景     

Vimentin在子宫内膜腺癌组织中的表达及其临床意义

目的探讨Vimentin在人子宫内膜腺癌中的表达及其临床意义。方法采用免疫组化方法及Western-blot方法研究子宫内膜腺癌组织及正常子宫内膜组织中Vimentin的表达。结果 Vimentin蛋白表达水平在子宫内膜癌组织中显著高于正常子宫内膜组织(P0.05)。Vimentin在子宫内膜癌组织的表达与年龄,FIGO分期,癌症分化程度,病灶大小以及肌层浸润深度密切相关(P0.05),并与雌激素受体(Estrogen Receptor,ER),孕激素受体(Progesterone Receptor,PR)呈负相关。结论 Vimentin在子宫内膜癌中过表达,提示其可能参与子宫内膜癌的发病机制。     

表皮生长因子受体检测方法

表皮生长因子受体(EGFR)是一种受体型酪氨酸激酶,在多种肿瘤中都有过表达,并与肿瘤的发生、浸润、转移、预后及患者生存期密切相关.多种方法可用于检测组织、血液、细胞中EGFR蛋白表达及其酪氨酸激酶活性,EGFR的检测将有助于肿瘤的靶向治疗.     

干扰表皮生长因子受体磷酸化过程对乳腺癌的抑制效应

目的 探讨干扰表皮生长因子受体(EGFR)的磷酸化过程对裸鼠乳腺癌移植瘤生长的影响及其作用机制.方法 建立裸鼠乳腺癌移植瘤模型,成型后随机分为Ad5-hSulf1组、Ad5-EGFP组和对照组,干预治疗后,测量计算移植瘤生长率,采用免疫组化法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR阳性表达,采用Western blot法检测各组裸鼠移植瘤hSulf-1、EGFR和p-EGFR蛋白表达.结果 Ad5-hSulf1组裸鼠注射治疗后第14天、21天和28天的肿瘤生长率[(165.9±23.8)％,(172.6±25.9)％,(377.3±30.5)％]明显小于同期的对照组,差异均具有统计学意义(t=12.153,21.247,14.587;P =0.000).Ad5-hSulf1组裸鼠移植瘤p-EGFR阳性表达率(46.7％)和蛋白表达[(52.7±7.4)％]明显低于Ad5-EGFR组和对照组,差异均有统计学意义(x2=8.146,t=7.384,7.587;P =0.004、0.000、0.000).结论 使用hSulf1基因抑制乳腺癌细胞的EGFR磷酸化过程,可产生明显的肿瘤抑制效应,对寻求肿瘤基因治疗的一个很有潜力的靶点具有很好的借鉴参考意义.     

血管内皮生长因子及其受体在子宫内膜异位症中的表达和意义

目的:研究血管内皮生长因子(Vascular endothelial growth factor,VEGF)及其受体(Vascular endothelial growth factor receptor1,VEGFR1)在子宫内膜异位症(内异症)患者子宫在位内膜、异位内膜及正常对照组内膜组织中的表达,探讨其在子宫内膜异位症中的作用机制.方法:采用免疫组织化学及Western blot方法检测34例异位症患者在位内膜、异位内膜(内异症组)及34例正常内膜(对照组)组织中VEGF及其受体VEGFR1蛋白的定位及表达.结果:异症组在位及异位子宫内膜组织腺上皮细胞及间质细胞中均有VEGF及VEGFR1蛋白表达,且均高于同期对照组内膜,差异有统计学意义;对照组分泌期内膜VEGF及VEGFR1蛋白表达高于增生期,呈现周期性变化,而内异症组在位及异位内膜VEGF及VEGFR1蛋白表达失去周期性变化,分泌期与增生期均高表达,差异无统计学意义.Western blot检测结果与免疫组化结果一致.结论:内异症患者在位及异位内膜组织中VEGF、VEGFR1蛋白高表达可能与内异症的发生发展有关.     

子宫内膜腺癌细胞系特异性结合短肽筛选及分析

目的和方法：用噬菌体随机12肽库对人子宫内膜腺癌细胞系(EAC)进行全细胞筛选,并通过特异性结合实验检验所筛选出的克隆的结合特异性。 结果： 经过5轮“吸附-洗脱-扩增”，噬菌体高度富集,并得到1个结合特异性较强的克隆。 结论： 利用噬菌体肽库可以简便、迅速地筛选出与EAC特异性结合的克隆，为进一步研制子宫内膜癌的靶向药物提供实验依据。     

表皮生长因子受体与他莫西芬耐药机制

雌激素受体及其信号通路在乳腺癌的发生发展中发挥着关键作用.到目前为止,抑制或阻断雌激素信号通路的内分泌治疗尤其是他莫西芬,仍是对雌激素受体阳性乳腺癌患者最有效的治疗手段之一.然而,他莫西芬的耐药问题直接影响了乳腺癌患者的治疗及预后.最近多项研究表明雌激素受体与表皮生长因子受体家族尤其是HER2介导的信号传导通路在多个点上相互交叉,彼此影响,与他莫西芬的耐药密切相关     

Epidermal growth factor receptor in human uterine tissues

Epidermal growth factor receptor (EGFR) was studied in human endometrium and myometrium collected throughout the menstrual cycle (five follicular, five luteal specimens) by immunohistochemistry and quantitative ligand binding. EGFR was principally present on the cell surface of glandular epithelium of the endometrium. Staining was no different between the follicular and luteal phases. There was more EGFR binding in endometrium than myometrium by quantitative ligand binding in membrane preparations: endometrium, median = 92.5 fmol/mg protein (range 25.3-294) n = 10; myometrium, median = 43.0 fmol/mg protein (range 23.4-57) n = 10. There was no difference in the level of binding in the follicular and luteal phases.     

Tumor-associated macrophages,epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma

It has been well established that tumor-associated macrophages (TAMs) play a tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However, the association with TAMs and the triple-negative phenotype (TNP) in EEC has not yet been reported. We used immunohistochemistry to examine the expression of CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186 cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2 amplification, and the association with TAMs count, EGFR expression, and triple-negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the TNP. It was associated with advanced stage disease (P < 0.0001), high grade disease (P < 0.0001), depth of myometrial invasion (P = 0.003), pelvic lymph node metastasis (P < 0.001), lymphovascular space invasion (P = 0.001), and EGFR expression (P = 0.032). Margin TAMs count was also significantly increased in the TNP-positive group, the EGFR-positive group, and the PR-negative group (P < 0.001, respectively). The TNP was associated with a significantly worse overall survival (OS) (log rank test, P = 0.018). The estimated 5-year OS of patients with TNP was 59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin TAMs, and the histopathological grades were significantly associated with OS. The TNP in EEC is associated with poor prognostic surgical–pathological factors, worse prognosis, as well as with high margin TAMs and overexpression of EGFR, which may serve as potential targeted therapies for the special phenotype in EEC.     

Epidermal growth factor receptors in endometrial adenomatosis

The expression of the epidermal growth factor receptors (EGFR) and of progesterone and estrogen receptors (PR and ER, respectively) was studied in 31 women of a reproductive age with endometrial adenomatosis. The receptor phenotype EGFR+PR-ER-, indicating mainly local regulation of the proliferative processes, was detected in adenomatous endometrium three times more often than in normal endometrium. The metabolic endocrine disorders were less frequent in patients with endometrial adenomatosis with EGFR, but the disease ran a more severe course in these patients, which was proven by more numerous diagnostic scrapings performed within the same period. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 45–49, January, 1999     

Epidermal growth factor receptor mutations in lung cancers

In 2004, two groups reported somatic mutations in the gene for the epidermal growth factor receptor (EGFR) in patients with non-small cell lung cancer (NSCLC), which were highly correlated with the clinical response to the anticancer drug, gefitinib. Since then, a tremendous amount of knowledge has accumulated, and sheds light on significant oncological properties as well as the clinical relevance of this mutation, which could be applicable to other malignancies. The EGFR mutations are distributed throughout the kinase domain, but a deletion in exon 19 and the point mutation L858R in exon 21 account for approximately 90%, which confer a greater response to gefitinib treatment, compared with other types of EGFR mutations. These EGFR mutations in the tyrosine kinase domain are seldom acquired in cancers of the other organs and the mutations preferentially involve a subset of lung cancers, which are clinicopathologically characterized by female sex, non-smoking, adenocarcinoma histology and East Asian ethnicity. In Japan, the EGFR mutations are detected in approximately 30% of overall NSCLC and approximately 40% of surgically resected adenocarcinomas. The morphological features of adenocarcinomas harboring the mutations were reported to be frequent in those with bronchioloalveolar features, but it is suggested that the cellular lineage of the putative original cells of the cancers refines the subset more clearly. In the present study the current knowledge of EGFR mutations is reviewed, insights from which raise many further questions, and thus suggest new directions for future research.     

Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer.

Overexpression of the epidermal growth factor receptor (EGFR) has been reported as an important molecular abnormality in human pancreatic cancer. There is in vitro evidence that simultaneous overproduction of one of its ligands, transforming growth factor alpha (TGF-alpha), might result in an autocrine loop with an increased proliferation signal. We analysed by immunocytochemical staining a retrospective series of human pancreatic cancers, chronic pancreatitis, and normal fetal and adult pancreatic tissues for the presence of TGF-alpha and epidermal growth factor (EGF). Ductal epithelial cells showed TGF-alpha immunoreactivity in both normal tissue and chronic pancreatitis, and 95 per cent of tumours showed strong immunoreactivity. In contrast, EGF immunoreactivity was not found in normal pancreas, but was expressed in 12 per cent of pancreatic carcinomas. Well-defined areas of EGF immunoreactivity in exocrine ducts showing reactive changes in pancreatitis might represent a benign response to tissue damage similar to that previously described in the gastric mucosa.     

Epidermal growth factor receptor - but not histamine receptor - is upregulated in seasonal allergic rhinitis

BACKGROUND: We were interested in exploring the molecular mechanisms underlying the observed difference in histamine (H) responsiveness between seasonal allergic rhinitic (SAR) and nonrhinitic (NR) subjects. We hypothesized that SAR subjects express higher nasal mucosal histamine receptor 1 (H1R) and 2 (H2R) levels than do NR subjects. In addition, we examined expression of genes involved in regulating the glandular response, including epidermal growth factor (EGF), EGF receptor (EGFR), and mucins (Muc5Ac and Muc5B). METHODS: Fourteen subjects, seven SAR and seven NR, were provoked during pollen season with doubling doses of H (0.125-8.0 mg/ml). Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Provocation was halted when NAR exceeded 150% of baseline. Prior to provocation, nasal scrapings were obtained and mRNA quantified using two-step real-time PCR. RESULTS: The mean PD50 (concentration of H producing a 50% increase in NAR) was significantly lower in the SAR than NR group (0.36 vs 1.32 mg/ml; P < 0.05). The ratio of relative gene copy numbers between the SAR and NR groups were as follows: H1R, 0.85 (P = 0.52); H2R, 0.67 (P = 0.35); EGF, 1.02 (P = 0.93), and EGFR, 103.5 (P < 0.05). CONCLUSIONS: There were no significant differences in H1R or H2R mRNA levels between SAR and NR subjects in-season, despite observed differences in H reactivity. SAR subjects, however, did show a significant elevation in EGFR expression, consistent with the observation of mucus hypersecretion in allergic rhinitis.     

Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone

Balla P, Moskovszky L, Sapi Z, Forsyth R, Knowles H, Athanasou N A, Szendroi M, Kopper L, Rajnai H, Pinter F, Petak I, Benassi M S, Picci P, Conti A & Krenacs T
(2011) Histopathology 59 , 376–389 Epidermal growth factor receptor signalling contributes to osteoblastic stromal cell proliferation, osteoclastogenesis and disease progression in giant cell tumour of bone Aims: Epidermal growth factor receptor (EGFR) is implicated in bone remodelling. The aim was to determine whether EGFR protein expression contributes to the aggressiveness and recurrence potential of giant cell tumour of bone (GCTB), an osteolytic primary bone tumour that can exhibit markedly variable clinical behaviour. Methods and results: Immunohistochemical analysis on tissue microarrays (TMA) of 231 primary, 97 recurrent, 17 metastatic and 26 malignant GCTBs was performed using TMA analysis software and whole digital slides allowing validated scoring. EGFR expression was restricted to neoplastic stromal cells and was significantly more frequent in recurrent (71 of 92; 77%) than in non‐recurrent GCTBs (86 of 162; 53%) (P = 0.002); and in clinicoradiologically aggressive (31 of 43; 72%) than latent (27 of 54; 50%) cases (P = 0.034). Detecting phosphotyrosine epitopes pY1068 and ‐pY1173 indicated active EGFR signalling, and finding EGFR ligands EGF and transforming growth factor‐α restricted to cells of the monocytic lineage suggested paracrine EGFR activation in stromal cells. In functional studies EGF supported proliferation of GCTB stromal cells, and the addition of EGF and macrophage‐colony stimulating factor promoted osteoclastogenesis. Conclusion: In GCTB, EGFR signalling in neoplastic stromal cells may contribute to disease progression through promoting stromal cell proliferation and osteoclastogenesis.