雌激素受体亚型ERα、ERβ在乳腺癌中的表达

目的研究雌激素受体亚型ERα、ERβ在不同乳腺组织中的表达及其在浸润性乳腺癌中与肿瘤病理参数和生物学标志物之间的关系。方法选取70例乳腺癌(其中8例原位癌、44例浸润性导管癌、18例浸润性小叶癌)、15例乳腺增生、15例正常乳腺组织石蜡标本,用免疫组织化学法检测ERα、ERβ、C-erbB-2的表达情况。结果 (1)乳腺癌组织中的ERα阳性表达率明显高于正常乳腺及乳腺增生组织;晚期乳腺癌患者ERα阳性表达率明显低于早期患者;C-erbB-2阳性患者的ERα阳性表达率明显减低。(2)乳腺癌组织中的ERβ阳性表达率明显低于正常乳腺及乳腺增生组织;在浸润性乳腺癌中淋巴结转移阳性者、C-erbB-2表达阳性者的ERβ阳性表达率明显高于对照组患者。结论 ERα在乳腺癌的发生发展中可能起到促进作用,ERα的阳性表达与一些预后良好因素相关。ERβ可能对维持乳腺组织的正常生理功能起着重要作用,其与某些预后不良因素可能相关。     

乳腺癌ER与病理学关系的探讨

对３２５例乳腺癌进行雌激素受体（ＥＲ）检测，结果提示年龄〉３５岁、肿瘤２￣５ｃｍ、ＴＮＭ分期Ⅱ期的浸润性非特殊型癌的ＥＲ阳性率最高（Ｐ〈０．０５）。ＥＲ阳性患者的淋巴转移度明显高于ＥＲ阴性乾（Ｐ〈０．０１）。此可为制定合理治疗方案、指导内分泌治疗及正确估计预后提供依据。     

Aggressive Prostate Cancer Is Prevented in ERαKO Mice and Stimulated in ERβKO TRAMP Mice

Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ERα or ERβ to play a protective role against prostate cancer, we bred transgenic mice lacking functional ERα or ERβ with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ERα knockout (KO) or ERβKO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ERαKO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ERβKO mice to 41%. Interestingly, immunohistochemical analysis showed ERα expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ERβ location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ERα vs. ERβ would result in prevention of advanced prostate cancer.     

胰腺癌中ERα变异体的表达

目的检测胰腺癌中雌激素受体α(ERα)不同变异体ERC4、ERD3、ERD5 mRNA的表达.方法采用免疫组化和RT-PCR检测技术,对50例胰腺癌和20例乳腺癌患者ERα的表达以及变异体ERC4、ERD3、ERD5 mRNA的表达进行检测.结果胰腺癌ERα蛋白的阳性率为32%.ERD3 mRNA在ER阳性胰腺癌表达低于阴性病例;ERC4 mRNA在ER阴性胰腺癌表达明显低于阳性病例(P < 0.05);ERD5 mRNA在ER阳性胰腺癌表达低于阴性病例.结论 ERα变异体的检出说明它们在胰腺癌发生过程中起一定的作用.在胰腺癌的发生过程中,ERα变异体mRNA的表达失控.     

ER stress: can the liver cope?

Hepatocytes contain abundant endoplasmic reticulum (ER) which is essential for protein metabolism and stress signaling. Hepatic viral infections, metabolic disorders, mutations of genes encoding ER-resident proteins, and abuse of alcohol or drugs can induce ER stress. Liver cells cope with ER stress by an adaptive protective response termed unfolded protein response (UPR), which includes enhancing protein folding and degradation in the ER and down-regulating overall protein synthesis. When the UPR adaptation to ER stress is insufficient, the ER stress response unleashes pathological consequences including hepatic fat accumulation, inflammation and cell death which can lead to liver disease or worsen underlying causes of liver injury, such as viral or diabetes-obesity-related liver disease.     

胰腺癌中ERα变异体的表达

目的检测胰腺癌中雌激素受体α(ERα)不同变异体ERC4、ERD3、ERD5mRNA的表达。方法采用免疫组化和RT-PCR检测技术,对50例胰腺癌和20例乳腺癌患者ERα的表达以及变异体ERC4、ERD3、ERD5mRNA的表达进行检测。结果胰腺癌ERα蛋白的阳性率为32％。ERD3mRNA在ER阳性胰腺癌表达低于阴性病例;ERC4mRNA在ER阴性胰腺癌表达明显低于阳性病例(P<0.05);ERD5mRNA在ER阳性胰腺癌表达低于阴性病例。结论ERα变异体的检出说明它们在胰腺癌发生过程中起一定的作用。在胰腺癌的发生过程中,ERα变异体mRNA的表达失控。     

食管癌组织ER、PR测定的临床意义

为探讨食管癌患者中的雌激素受体 (ER)和孕激素受体 (PR)情况 ,我们对 2 6例患者作了 ER和 PR监测。现报告如下。临床资料 :本组男 18例 ,女 8例 ;年龄 35～ 77岁。切除标本与常规病理检查同时送检 ,结果 ER、PR阳性 19例 ,弱阳性 3例 ,阴性 4例。ER,PR阳性的 19例中 ,18例为分化较好的鳞状上皮癌 ,1例为鳞腺癌。37个淋巴结中查见 4枚转移癌 (3例 ) ,弱阳性和阴性的 7例中 ,病理结果显示肿瘤细胞呈中度分化 5例 ,低度分化 2例 (其中 1例为贲门癌累及食管下段 )。 7例中查见 2 6个淋巴结 ,其中 2 0个查到转移癌。本组 1例 35岁男性 ,…     

Occurrence and cellular distribution of estrogen receptors ERα and ERβ in the testis and epididymal region of roosters

Estrogen signaling is required for the maintenance of male reproductive function and is mediated by the estrogen receptors ERα and ERβ. These receptors are widely distributed in mammalian reproductive tissues, but information is limited in non-mammalian species including birds. The aim of this study was to investigate the occurrence and cellular distribution of ERα and ERβ in the testis and epididymal region of roosters. The results showed for the first time that ERβ was the predominant receptor detected in the testis, being expressed in the somatic and some germ cells. Within the epididymal region, ERβ was strongly expressed in all segments, whereas the most intense reaction for ERα was found in the distal efferent ductules. The differential expression of ERα and ERβ within the rooster testis and epididymal region suggests that these organs may be a target for different actions of estrogen.     

Estrogen receptor (ER) β expression in oligodendrocytes is required for attenuation of clinical disease by an ERβ ligand

Treatment of experimental autoimmune encephalomyelitis (EAE) mice with the estrogen receptor (ER) β ligand diarylpropionitrile (DPN) has been shown to have neuroprotective effects via stimulation of endogenous myelination. The direct cellular mechanisms underlying the effects of this ERβ ligand on the central nervous system are uncertain because different cell types in both the peripheral immune system and central nervous system express ERs. ERβ is the target molecule of DPN because DPN treatment fails to decrease EAE clinical symptoms in global ERβ-null mice. Here we investigated the potential role of ERβ expression in cells of oligodendrocyte (OL) lineage in ERβ ligand-mediated neuroprotection. To this end, we selectively deleted ERβ in OLs using the well-characterized Cre-loxP system for conditional gene knockout (CKO) in mice. The effects of this ERβ CKO on ERβ ligand-mediated neuroprotective effects in chronic EAE mice were investigated. ERβ CKO in OLs prevented DPN-induced decrease in EAE clinical disease. DPN treatment during EAE did not attenuate demyelination, only partially improved axon conduction, and did not activate the phosphatidylinositol 3-kinase/serine-threonine-specific protein kinase/mammalian target of rapamycin signaling pathway in ERβ CKO mice. However, DPN treatment significantly increased brain-derived neurotrophic factor levels in ERβ CKO mice. These findings demonstrate that signaling through ERβ in OLs is essential for the beneficial myelination effects of the ERβ ligand DPN in chronic EAE mice. Further, these findings have important implications for neuroprotective therapies that directly target OL survival and myelination.Multiple sclerosis (MS) is an inflammatory, demyelinating neurodegenerative disease characterized by physical, and often cognitive, deficits that can progress to severe debilitation. Although current MS treatments exist in the form of immunomodulatory or immunosuppressive agents, these treatments fail to halt disease progression and are not directly neuroprotective.Building on a wealth of research supporting a role for estrogens in neuroprotection, we have demonstrated that treatment of experimental autoimmune encephalomyelitis (EAE) mice with the estrogen receptor (ER) β ligand 2,3-bis(4-Hydroxyphenyl)-propionitrile (DPN) attenuates clinical disease, neurodegeneration, and axon demyelination and improves axon conduction (1–4). Notably, these effects were observed with both prophylactic and therapeutic treatment regimens, and they occurred in the presence of peripheral cytokine production and central nervous system (CNS) inflammation. Evidence of direct neuroprotection by an ERβ ligand is welcomed, because it circumvents ERα-mediated adverse effects of synthetic estrogens [i.e., increased breast and uterine endometrial growth in females and feminizing effects in males (5)].Because ERs are present in various cell types in the peripheral immune system and CNS, including cells of oligodendrocyte (OL) lineage, it is difficult to assess which cell type(s) mediate ERβ ligand-conferred neuroprotection (6). ERβ is the target molecule of DPN: DPN treatment fails to decrease EAE clinical symptoms in global ERβ-null mice (4). Although informative, such studies do not elucidate the cell type(s) on which DPN acts. We have recently demonstrated that therapeutic treatment with DPN increases mature OL numbers, remyelination-induced callosal conduction, and phosphorylated ERβ levels in OLs, and that it activates the phosphatidylinositol 3-kinase (PI3K)/serine-threonine-specific protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway, a pathway implicated in OL survival, differentiation, and axon myelination (1, 7, 8). Taken together with the pronounced, functional improvement in endogenous myelination observed in DPN-treated chronic EAE mice, a direct effect on ERβ in OLs may mediate ERβ ligand-induced myelination/remyelination improvement and neuroprotection. To test this hypothesis, ERβ was selectively deleted from OLs using the well-characterized Cre-loxP recombination system for conditional gene knockout (CKO) in mice (9–12). The Olig2,ERβ CKO mice that resulted from crossing ERβ^flox/flox and Olig2-tva-Cre mice were viable and displayed normal behavior and gross CNS anatomy; hence, the effect of ERβ CKO in OLs on ERβ ligand-induced neuroprotection in chronic EAE mice was investigated. ERβ CKO in OLs prevented DPN-induced attenuation of clinical disease and demyelination and failed to activate the PI3K/Akt/mTOR signaling pathway. However, DPN treatment in Olig2,ERβ CKO mice partially improved axon conduction and reduced axonal loss and, as in WT mice, significantly increased BDNF levels. These findings reveal a direct action of the ERβ ligand DPN on ERβ in OLs in DPN-induced myelination/remyelination effects within a chronic mouse model of MS.     

ERβ和VEGF在大肠癌中的表达及临床意义

目的:探讨雌激素受体β(ERβ)、血管内皮生长因子(VEGF)在大肠癌组织中的表达以及与大肠癌分化程度之间的关系.方法:应用免疫组织化学SP法,检测45例大肠癌中ERβ,VEGF的表达,并以10例正常大肠黏膜组织作对照,分析大肠癌组织中ERB与VEGF的表达与大肠癌的关系.结果:45例大肠癌组织中,ERβ阳性23例(51.11%),VEGF阳性33例(73.33%).ERβ和VEGF的表达与肿瘤的分化程度有关(P= 0.024,P=0.005),而与肿瘤的临床分期无关(P=0.289,P=0.173).ERB阳性组中,VEGF的表达明显低于ERβ阴性组(56.52% vs 90.90%,P<0.05).结论:ERβ的阳性表达与大肠癌的发生、发展和预后密切相关,可联合VEGF作为有价值的肿瘤标记和预后指标.     

Expression patterns of ERα66 and its novel variant isoform ERα36 in lactotroph pituitary adenomas and associations with clinicopathological characteristics

Pituitary - The regulatory effects of estradiol on pituitary homeostasis have been well documented. However, the expression patterns of ERα66 and ERα36 and their correlations with the...     

青年人胃癌P53 PCNA ER及PR的表达

青年人胃癌Ｐ５３ＰＣＮＡＥＲ及ＰＲ的表达左大镒肖宝芝朱德为Ｓｕｂｊｅｃｔｈｅａｄｉｎｇｓｓｔｏｍａｃｈｎｅｏｐｌａｓｍｓ／ｍｅｔａｂｏｌｉｓｍ；ｐｒｏｔｅｉｎｐ５３／ｍｅｔａｂｏｌｉｓｍ；ｐｒｏｌｉｆｅｒａｔｉｎｇｃｅｌｎｕｃｌｅａｒａｎｔｉｇｅｎ...     

乳腺癌组织中ERβcx的表达及意义

目的探讨雌激素受体βcx（ERβcx）在乳腺癌发生、发展中的作用。方法采用免疫组化SP法测定52份乳腺癌组织标本中ERβcx表达，分析其与临床病理参数的关系。结果本组ERβcx阳性25例（48．07％），仅与淋巴结转移有关（P〈0．05）。结论ERβcx高表达可促进乳腺癌进展，对判断预后有一定价值。     

TAM对人肝癌细胞增殖及ER表达的影响

目的研究他莫昔芬（TAM）对人肝癌HepG2细胞增殖和雌激素受体（ER）表达的影响。方法将7．5、15、30μmol／L的TAM分别作用于HepG2细胞（观察组）,对照组不加TAM,每孔加入1×10^5／ml细胞0．1ml,培养24、48、72h,采用MTT法测定HepG2抑制率;细胞免疫组化染色观察HepG2细胞ER的表达。结果TAM作用后HepG2细胞增殖随浓度增加及处理时间延长,细胞抑制率增加。结论TAM可抑制肝癌细胞增殖,其机理可能为降低ER表达。     

Anxiolytic effects and neuroanatomical targets of estrogen receptor-β (ERβ) activation by a selective ERβ agonist in female mice

The dichotomous anxiogenic and anxiolytic properties of estrogens have been reported to be mediated by two distinct neural estrogen receptors (ER), ERα and ERβ, respectively. Using a combination of pharmacological and genetic approaches, we confirmed that the anxiolytic actions of estradiol are mediated by ERβ and extended and these observations to demonstrate the neuroanatomical targets involved in ERβ activation in these behavioral responses. We examined the effects of the biologically active S-enantiomer of diarylpropionitrile (S-DPN) on anxiety-related behavioral measures, the corresponding stress hormonal response to hypothalamo-pituitary-adrenal axis reactivity, and potential sites of neuronal activation in mutant female mice carrying a null mutation for ERβ gene (βERKO). S-DPN administration significantly reduced anxiety-like behaviors in the open field, light-dark exploration, and the elevated plus maze (EPM) in ovariectomized wild-type (WT) mice, but not in their βERKO littermates. Stress-induced corticosterone (CORT) and ACTH were also attenuated by S-DPN in the WT mice but not in the βERKO mice. Using c-fos induction after elevated plus maze, as a marker of stress-induced neuronal activation, we identified the anterodorsal medial amygdala and bed nucleus of the stria terminalis as the neuronal targets of S-DPN action. Both areas showed elevated c-fos mRNA expression with S-DPN treatment in the WT but not βERKO females. These studies provide compelling evidence for anxiolytic effects mediated by ERβ, and its neuroanatomical targets, that send or receive projections to/from the paraventricular nucleus, providing potential indirect mode of action for the control of hypothalamo-pituitary-adrenal axis function and behaviors.     

乳腺癌患者50例ER、PR检测结果分析

为了探讨雌激素受体 (ER)、孕激素受体 (PR)对乳腺癌诊断、治疗的意义 ,笔者采用高敏感度 ABC免疫组化法检测了 5 0例乳腺癌患者的 ER、PR,报告如下。临床资料 :5 0例均选自 1980～ 1995年来我院行乳腺癌手术切除的患者 ,且临床和病理资料完整。 5 0例均予随访 ,随访时间 4～ 19年 ,5 0例患者均为女性 ,其中年龄小于 40岁 7例 ,～ 5 0岁 15例 ,～ 6 0岁 2 0例 ,～ 70岁 8例。 5 0例中未闭经或闭经不足 1年 2 5例 ,闭经 1年以上 2 5例。方法 :ER和 PR抗血清由上海内分泌研究所提供 ,ABC试剂盒为美国 Veclor公司产品 ,乳腺癌切除标本…