Increased Midkine and Estrogen Receptor-β Expression in Human Non-Small Cell Lung Cancer

Objective： Midkine （MK）, a new member of the heparin-binding growth factor family, has been found recently to have a high expression level in many tumor specimens including lung carcinoma. Estrogens may be involved in lung carcinogenesis, and estrogen receptors, mainly estrogen receptor-β （ER-β）, are present and functional in normal lung and tumor cell lines and tissues. In addition, estrogens and growth factors may promote the progression of human non-small cell lung cancer （NSCLC）. Previously, we have immunohistochemically demonstrated that MK and ER-β proteins were overexpressed in NSCLC and their expression levels were both significantly negatively correlated with the pathological classification. The purpose of this study was to further verify their expression and its correlation with NSCLC. Methods： Taking NSCLC tissues and their corresponding paraneoplastic and normal lung as research objects, we further examined the expression of MK and ER-β by meas of RT-PCR, in situ hybridization and Western blot analyses at the levels of messenger RNA （mRNA） and protein, respectively. Results： The increased MK and ER-β mRNA expression was found in NSCLC by RT-PCR and in situ hybridization analyses. Furthermore, Western blot analysis also displayed increased expression of MK and ER-β proteins in NSCLC. Finally, their correlation analysis at the levels of mRNA and protein expression in NSCLC demonstrated that MK protein level was significantly correlated to estrogen receptor-β （P〈0.01, rs=0.535）; in spite of their correlation at the mRNA level, there was no remarkable difference between MK and ER-β （P〉0.05, rs=0.178）. Conclusion： All these results in the present study confirmed that MK and ER-β were overexpressed in human NSCLC.

Expression of voltage.gated sodium channel Nav1.5 in non.metastatic colon cancer and its associations with estrogen receptor(ER)-βexpression and clinical outcomes

Background: Voltage-gated sodium channel 1.5(Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β(ER-β)expression in non-metastatic colon cancer patients receiving radical resection.Methods: A total of 269 consecutive patients with pathologically confirmed stages Ⅰ-Ⅲ colon cancer who underwent radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry(IHC)on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coefficient, Chi square test or Fisher's exact test, logistic regression, log-rank test, and Cox proportional hazards models.Results: We found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues(5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001).The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio(OR) = 2.980;95% confidential interval(CI)1.163-7.632; P = 0.023] and high ER-β expression(OR = 2.808; 95% CI 1.243-6.343;p = 0.00 3). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival(DFS) rate in colon cancer patients(77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor(76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression[hazard ratio(HR) = 2.738; 95% CI 1.100-6.819;P = 0.030] and lymph node metastasis(HR = 2.633; 95% CI 1.632-4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients.Conclusions: High expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.

phytoestrogens/insoluble fibers and colonic estrogen receptor β: randomized, double-blind, placebo-controlled study

AIM:To assess the safety and effect of the supplementation of a patented blend of dietary phytoestrogens and insoluble fibers on estrogen receptor (ER)-β and biological parameters in sporadic colonic adenomas. METHODS:A randomized, double-blind placebo-controlled trial was performed. Patients scheduled to undergo surveillance colonoscopy for previous sporadic colonic adenomas were identified, and 60 eligible patients were randomized to placebo or active dietary intervention (ADI) twice a day, for 60 d before surveillance colonoscopy. ADI was a mixture of 175 mg milk thistle extract, 20 mg secoisolariciresinol and 750 mg oat fiber extract. ER-β and ER-α expression, apoptosis and proliferation (Ki-67 LI) were assessed in colon samples. RESULTS:No adverse event related to ADI was recorded. ADI administration showed a significant increases in ER-β protein (0.822 ± 0.08 vs 0.768 ± 0.10, P = 0.04) and a general trend to an increase in ER-β LI (39.222 ± 2.69vs 37.708 ± 5.31,P = 0.06), ER-β/ER-α LI ratio (6.564 ± 10.04 vs 2.437 ± 1.53, P = 0.06), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (35.592 ± 14.97 vs 31.541 ± 11.54, P = 0.07) and Ki-67 (53.923 ± 20.91 vs 44.833 ± 10.38, P = 0.07) approximating statistical significance. A significant increase of ER-β protein (0.805 ± 0.13 vs 0.773 ± 0.13,P = 0.04), mRNA (2.278 ± 1.19vs 1.105 ± 1.07, P < 0.02) and LI (47.533 ± 15.47 vs 34.875 ± 16.67,P < 0.05) and a decrease of ER-α protein (0.423 ± 0.06vs 0.532 ± 0.11,P < 0.02) as well as a trend to increase of ER-β/ER-α protein in ADI vs placebo group were observed in patients without polyps (1.734 ± 0.20 vs 1.571 ± 0.42, P = 0.07). CONCLUSION:The role of ER-β on the control of apoptosis, and its amenability to dietary intervention, are supported in our study.

The Effect of GnRHa Induced Superovulation on Endometrial Morphology and Estrogen Receptor and Progesterone Receptor in Mouse

To evaluate the effect of GnRHa induced superovulation protocol on endometrial morphology and function. Material & Methods Forty ICR mice were randomly allocated into 4 groups, among them, 2 experimental groups were injected with GnRHa+HMG+hCG, another 2 groups were given saline of same volume as control group. The uterine tissues were investigated at 24 h and 48 h after administration (experimental group) or ovulation (control group).The endometrial thickness, the size of gland and glandular lumen, the total area of glandular cells, the average height of glandular epithelium were measured from routine histological slides using computerized image analysis. The SP immunohistochemistry techniques with monoclonal antibodies were employed to semi quantitatively analize the estrogen receptor (ER) and progesterone receptor (PR) in glandular cells. Results The endometrial thickness was not significantly different between experimental groups and control groups at 24 h and 48 h (P>0.05).The average area, perimeter, maximal diameter of single gland and glandular lumen, the total area, average height of glandular epithelium in experimental groups were significantly smaller than those of in control groups at equivalent time stages (all P<0.01). The asynchronous development of gland epithelium and stroma cells, namely, pesudostratified glandular epithelium and predecidual changes of stroma cells were seen at same time in experimental groups. The positive percentage (%) and expression intense of ER and PR in glandular epithelium cells were significantly lower in experimental groups than in control groups (P<0.05). Conclusion The protocol with GnRHa had a negative effect on endometrial histological structure and down regulated the express of ER and PR, suggesting that this protocol effect on the endometrial morphology and function and could not facilitate the formation of a physiologic endometrium completely, which may be one of the causes of low pregnancy rates.

Association between estrogen receptor β gene Rsa1 polymorphism and depressive disorder in peri-menopausal and menopausal women

Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four peri-menopausal and menopausal women with depressive disorder met ICD-10 and CCMD-3 assessment criteria for depressive disorder were recruited. ERβ gene Rsa1 polymorphism was analyzed with PCR-RFLP. Serum levels of estrogen, FSH and LH were measured by magnetism-ELISA. Results: The respective frequency of ERβ gene Rsa1 polymorphism was no significant difference between women with depressive disorder and the healthy women (χ 2=1.106,P>0.05). The serum level of estrogen was lower in women with depressive disorder than in the healthy women (P<0.05). No difference was found for FSH and LH between two groups. Conclusion: ERβ gene Rsa1 polymorphism may be not associated with depressive disorder in the peri-menopausal and menopausal women. The serum level of estrogen is associated with depressive disorder in the peri-menopausal and menopausal women.

Effects of Estrogen on ER, NGF, and ChAT Expression in Cerebellum of Aging Female Sprague-Dawley Rat

This article discusses the effects of estrogen on the expression of estrogen receptor （ER）, nerve growth factor （NGF）, and choline acetyltransferase （CHAT） in the cerebellum of rats. The model of aging female rat was established to study the expression and distribution of ER, NGF, and ChAT in the cerebellum following 17β-estradiol treatment using the technique of immunohistochemical ultrasensitive SP in sprague-dawley rat. The immunoreactive productions were distributed in stratum Purkinje cell, nucleus dentatus, nucleus interpositus, and nucleus fastigii of cerebellum, and the ER positive production was mainly located in the plasma, cytoplasmic membrane, and neurite, and also existed in nucleus. The general tendency of the expression of ER, NGF, and ChAT positive production in the cerebellum cortex and nuclei of aging rat significantly decreases, while the intensity and quantity of the immunoreactive production ascends predominantly after 17β-estradiol treatment. Simultaneously, the positive neurite of Purkinje cell shows a similar tendency. The above- mentioned results suggest that the estrogen upregulates the expression of NGF and CHAT, and plays a vital role in sustaining and protecting the structure and function of cerebellum neurons. Furthermore, the similarity of their changing tendency implies that they were correlated and cooperated during the course in effect of estrogen on cerebellum. It also showed that the action of estrogen in cerebellum could be via genomic and nongenomic mechanism.

Estrogen and insulin synergistically promote endometrial cancer progression via crosstalk between their receptor signaling pathways

Objective: Despite evidence that estrogens and insulin are involved in the development and progression of many cancers, their synergistic role in endometrial carcinoma(EC) has not been analyzed yet.Methods: Here, we investigated how estrogens act synergistically with insulin to promote EC progression. Cell growth in vitro and in vivo, effects of estradiol and insulin on apoptosis and cell cycle distribution, and expression and activation of estrogen receptor(ER), insulin receptor(InsR), and key proteins in the PI3K and MAPK pathways were examined after combined stimulation with estradiol and insulin.Results: Compared to EC cells treated with estradiol or insulin alone, those treated with both estradiol and insulin exhibited stronger stimulation. Estradiol significantly induced phosphorylation of InsR-β and IRS-1, whereas insulin significantly induced phosphorylation of ER-α. In addition, treatment with both insulin and estradiol together significantly increased the expression and phosphorylation of Akt, MAPK, and ERK. Notably, InsR-β inhibition had a limited effect on estradiol-dependent proliferation,cell cycle, and apoptosis, whereas ER-α inhibition had a limited insulin-dependent effect, in EC cell lines. Insulin and estradiol individually and synergistically promoted EC xenograft growth in mice.Conclusions: Estrogen and insulin play synergistic roles in EC carcinogenesis and progression by activating InsR-β and ER-α,promoting a crosstalk between them, and thereby resulting in the activation of downstream PI3K/Akt and MAPK/ERK signaling pathways.

The expression of estrogen receptors in thyroid cancer and its significance

Objective The study aimed to detect the expression of estrogen receptors(ERs) in thyroid cancer and investigate the correlation between their expression and clinical features and different pathological types.Methods The expression of ERs in 56 samples of thyroid cancer tissues was detected by an immunochemical approach. The expression of ERs in thyroid cancer tissues and different pathological types were analyzed using the χ~2 test. Results The number of cases with positive expression of ER in thyroid cancer tissues was 36. The number of papillary thyroid cancers(PTCs) was 48, with positive expression of ERs in 32 cases. The number of follicular thyroid cancers was 4, with positive expression of ERs in 2 cases. The number of medullary thyroid cancers was 4, with negative expression of ERs in all cases. The difference between the expression and different pathological types showed statistical significance. The expression of ERs showed no correlation with sex, age, or TNM stage, with no statistical significance. However, the expression of ERs was correlated with metastasis of lymph nodes, which had statistical significance. The expression of ERs was negatively correlated with pathological types and metastasis of lymph nodes. The correlated coefficient index was –0.313 and –0.334, respectively. Conclusion The expression of ERs showed no correlation with sex, age, or TNM stage, but was negatively correlated with pathological types and metastasis of lymph nodes.

NDRG2调控IRE1α-XBP1介导内质网应激逆转ER+乳腺癌他莫昔芬耐药

他莫昔芬(tamoxifen,TAM)作为雌激素受体阳性(estrogen receptor,ER+)乳腺癌的一线化疗药物使大多数患者受益,但原发性和继发性耐药问题严重影响临床治疗效果。深入研究ER+乳腺癌TAM耐药机制,改善治疗效果是当前亟待解决的问题。抑癌因子NDRG2(N-myc downstream regulated gene 2,NDRG2)在肿瘤发生发展中发挥重要作用,但是否参与ER+乳腺癌TAM耐药尚不清楚。本研究旨在探明NDRG2在ER+乳腺癌TAM耐药中发挥的作用和机制。通过RT-PCR与免疫印迹分析对比TAM敏感型和耐药型ER+乳腺癌细胞发现,NDRG 2的mRNA转录水平和蛋白质翻译水平在TAM耐药细胞中表达显著下调,且与耐药能力负相关(P<0.001);CCK-8细胞毒性实验和软琼脂克隆形成实验证实,在耐药细胞中过表达NDRG2可显著降低TAM药物半抑制浓度IC 50和软琼脂克隆形成率(P<0.001),逆转耐药表型。分子机制上,X-box结合蛋白1(X-box binding protein 1,XBP1)mRNA剪切实验与内质网相关降解(endoplasmic-reticulum associated degradation,ERAD)报告蛋白的结果显示,过表达NDRG2可增强耐药细胞中剪切型XBP1s mRNA转录与ERAD报告蛋白CD3ε-YFP表达(P<0.001),引发耐药细胞内质网强应激反应;免疫印迹检测结果显示,过表达NDRG2可显著提高耐药细胞中内质网应激感受器肌醇需要激酶1α(inositol requiring enzyme 1,IRE1α)的磷酸化水平及其下游因子,例如内质网EIP辅助因子(endoplasmic reticulum-localized DnaJ 4,ERdj4)、PKR蛋白激酶的细胞抑制剂(cellular Inhibitor of the PKR protein kinase,P58 IPK)、α甘露糖苷酶样应激蛋白(er degradation enhancingαmannosidase likeprotein,EDEM)和蛋白质二硫键异构酶家族A成员5(protein disulfide isomerase family a member 5,PDIA5)的表达水平(P<0.001)。小鼠异种移植瘤研究进一步证实,在耐药细胞中过表达NDRG2可增强TAM治疗效果,显著抑制耐药移植瘤生长(P<0.001)。以上研究结果表明,通过提高耐药细胞中NDRG2表达,增强TAM治疗引发的内质网强烈应激,可逆转ER+乳腺癌细胞耐药性,改善TAM治疗效果。研究结果为解决ER+乳腺癌TAM耐药问题提供了新的思路和有价值的潜在药物靶点。

Studies of the Expression of Estrogen Receptor Gene in the Rat Uterus during the Estrous Cycle and Periimplantational Period

The correlation or serum estradiol concentrstion and uterine estrogen receptor (ER) gene expression (ERn and ERc quantitated by Dextrsn Coat Charcoal assay and ER mRNA by Northern blotting) was studied during the rat estrous cycle and early Pregnant stage (dl-d10). The ER gone expression was up - regulated by estrogen and the levels of ER mRNA synchronized with the changes of ER protein, suggesting that estrogen influenced the trsnscriPtional step of the ER gene. Post-coitum ER expression increased with the serum estrsdiol progressively, reached a peak on d4-ds (Just before implantation), but drastically dropped to the nadir on d6-d7 (during implantation) and then recovered. It was of interest to discover that ER mRNA level in the nonimplantstion sites (NIS) of uterus was much higher than that in the implantstion sites (IS).

Correlation of Hormonal Receptors Estrogen Receptor, Progesterone Receptor and Her-2/Neu with Tumor Characteristics in Breast Carcinoma: Study of 100 Consecutive Cases

Introduction-Breast cancer is the most common cancer and leading cause of death in women. In India, its incidence is rapidly rising over last few decades. Present study is aimed to study the pattern of expression of hormonal receptors and Her-2/neu in invasive breast carcinoma and to correlate estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu expressions with various clinicopathological parameters. Material and methods: The present study was carried out in Department of Pathology, S.C.B. Medical College, Cuttack in the year 2013 taking consecutive 100 cases. Routine H&E staining for histological diagnosis and IHC analysis for ER, PR and Her 2/neu was carried out in all 100 cases of breast malignancies. Results: 99% of cases are invasive breast carcinoma, not otherwise specify (IDC-NOS). The age ranges from 23 years to 72 years. Majority of tumors are of grade 2 (70%) followed by grade 3 (30%). ER PR and Her-2/neu expression are seen in 45%, 35% and 30% respectively. Triple negative cases comprise 35%. Higher number of grade 2 tumor shows ER, PR positivity as compared to grade 3 tumors. Her-2/neu expression does not show any significant correlation with age or lymph node status of the patient. Conclusion: ER and PR expression in breast cancers in the current study are found to be comparable to the findings of other authors, but the frequency of HER-2/neu expression is slightly higher. Significant correlation is observed between hormonal receptor status and the grade of the tumor. Inverse relationship is found between Her-2/neu expression and ER, PR receptor status. Her-2/neu expression is increased with size and high grade of tumor.

绿鳍马面鲀ERα基因部分cDNA序列克隆及其表达研究

雌二醇是与生殖相关的重要的性类固醇激素之一,它与雌激素受体相结合作用于靶器官从而发挥生物活性。为进一步阐明绿鳍马面鲀雌激素受体α(Estrogen receptorα,ERα)的生理功能提供了科学依据,同时也为其人工繁育提供一定的理论基础,作者利用简并引物扩增得到绿鳍马面鲀(Navodon septentrionalis)ERα部分cDNA序列,共1410bp,编码470个氨基酸。通过半定量RT-PCR技术分别检测了其在雌鱼、雄鱼中各组织的表达情况,结果表明ERα在雌鱼体内的表达较雄鱼更广泛,在雌鱼垂体、心脏和卵巢的表达量最高,在雄鱼的垂体、肝脏、肾脏、精巢也有较高的表达。采用实时定量RT-PCR技术,分析了ERα在性腺中的周年表达情况,卵巢中ERαmRNA在5月表达量最高,7月最低:精巢中在5月最低,9月最高。该项研究表明ERα与绿鳍马面鲀生殖周期存在密切关联,提示在性腺发育过程中发挥一定作用。

整体原位杂交检测ERα基因在小鼠胚胎发育中的表达

为制备地高辛标记的小鼠雌激素受体α(ERα)RNA探针,用其研究ERα在小鼠胚胎发育过程中的表达。通过RT-PCR,获得ERα基因片段,构建ERα/pGEM-3Z重组质粒,分别用HindⅢ和EcoRⅠ进行酶切得到线性化DNA片段,以T7和Sp6聚合酶合成地高辛标记的正反义RNA探针,然后通过胚胎整体原位杂交技术分析ERα在小鼠胚胎中的表达。结果构建了ERα/pGEM-3Z质粒,获得高效价的正反义dig-ERαRNA探针。运用该探针检测到ERα在10.5dpc胚胎的前脑、脊神经管、生殖嵴、肢芽及颌弓中表达,在13.5dpc胚胎的端脑、中脑、脊髓、肢芽及生殖系统中表达,为进一步研究ERα在小鼠胚胎发育中的功能打下了基础。

育麟颗粒对排卵障碍大鼠下丘脑神经元ERα表达的影响

目的:通过观察育麟颗粒对排卵障碍大鼠下丘脑弓状核神经元ERα表达的影响,探讨育麟颗粒对肾虚排卵障碍促排卵的可能机制。方法:大鼠肌注氢化可的松造模后,随机分为模型组、西药对照组、育麟颗粒低、中、高剂量组,检测受试大鼠体重变化情况、卵巢的卵泡数目、黄体数目、下丘脑弓状核雌激素受体α(ERα)表达等指标。结果:①育麟颗粒各剂量组体重明显升高,肾阳虚症状明显恢复,与模型组相比有显著性差异(P<0.01)。②育麟颗粒各剂量组发育卵泡数和黄体数目均显著高于模型组。③育麟颗粒各剂量组大鼠下丘脑弓状核ERα表达水平均显著高于模型组(P<0.01)。结论:育麟颗粒对于排卵障碍的治疗,是通过多途径和多靶点作用的。在对机体的整体调节上育麟颗粒明显优于克罗米芬。

ERβ在乳腺癌组织中的表达及与临床病理因素的关系

目的 探讨ERβ在乳腺癌组织中的表达及其与临床病理因素的关系。 方法 采用免疫组化S -P法测定 97例原发性乳腺癌组织中ERα、ERβ和PR的表达 ,并与生化法测得的ER、PR及临床病理指标作对比分析。 结果 ERβ在原发性乳腺癌组织中阳性表达率为 62 .9% ( 61/ 97)。ERβ与ERα的表达无相关性 (P >0 .0 5 )。ERα、生化ER、PR及免疫组化PR均阴性表达的乳腺癌组织内ERβ阳性表达率为 83 .3 % ( 10 / 12 )。ERβ阳性表达与组织学分级呈负相关 (P <0 .0 1)。无腋淋巴结转移者的ERβ阳性表达率为 81.6% ( 3 1/ 3 8) ,有腋淋巴结转移者的ERβ阳性表达率为 5 0 .8% ( 3 0 / 5 9) ,两者具有非常显著性差异 (P <0 .0 1) ,且ERβ阳性表达与腋淋巴结转移呈负相关。ERβ表达与患者年龄、肿瘤大小、临床分期、月经状况和病理类型无明显相关 (P >0 .0 5 )。结论 ERβ与ERα、PR一样也为细胞核受体。原发性乳腺癌组织内亦有ERβ表达。在原发性乳腺癌组织内ERβ阳性表达与组织学分级和腋淋巴结转移呈负相关。ERβ与ERα的表达无相关性 ,不能通过ER、PR及ERα联合测定来取代ERβ的检测。

逍遥丸合六味地黄丸对原因不明月经过少子宫内膜细胞ER、VEGF和KDR表达影响

探讨逍遥丸合六味地黄丸治疗原因不明月经过少的机理。原代培养原因不明月经过少病人的子宫内膜,采用免疫细胞化学进行细胞鉴定。空白对照组,高剂量组,中剂量组,低剂量组,雌激素组。免疫蛋白质斑迹法观察子宫内膜细胞的雌激素受体(ER)、血管内皮生长因子(VEGF)及其受体(KDR)表达改变。逍遥丸合六味地黄丸能增强子宫内膜细胞的ER、VGER和KDR表达。逍遥丸合六味地黄丸可能通过提高子宫内膜组织中ER、VEGF和KDR治疗原因不明月经过少。

ER、PR、VEGF及其受体在原因不明月经过少发病机制中的作用

目的:通过对子宫内膜组织中雌激素受体(ER)、孕激素受体(PR)、血管内皮生长因子((VEGF)及其受体(KDR)表达的研究,探讨原因不明月经过少的发病机制。方法:2004年9月至2005年12月重庆医科大学附属第一医院以前瞻性方法观察月经过少组(观察组)和正常月经组(对照组)患者各40例,采用酶联免疫测定法,测定两组血清6项性激素,包括卵泡刺激素(FSH)、黄体生成素(LH)、雌激素(E2)、催乳素(PRL)、孕酮(P)及睾酮(T),通过免疫组化半定量测定两组子宫内膜组织中ER、PR、VEGF、KDR的表达水平。结果:两组血清性激素水平FSH、LH、E2、PRL、P及T差异无显著性意义(P>0.05);观察组子宫内膜ER、VEGF和KDR的表达明显低于对照组(P值分别为<0.05);两组子宫内膜腺上皮细胞PR的表达差异无显著性意义(P>0.05)。结论:子宫内膜组织中ER、VEGF和KDR的异常表达可能导致原因不明的月经过少。

新型雌激素受体ER-α36与乳腺癌

雌激素受体(estrogen receptor,ER)是诊断和治疗乳腺癌的分子标志和靶点.雌激素受体包括ER-α和ER-β,其中ER-α有ER-α66、ER-α46和ER-α36三种亚型.ER-α36作为新型雌激素受体,参与膜起始的雌激素信号或非基因组雌激素信号转导,在肿瘤细胞的增殖、分化、侵袭和转移等过程中发挥作用.胃癌、子宫内膜腺癌、前列腺癌、尤其是乳腺癌的发生发展与ER-α36密切相关.本文介绍了ER-α36的结构域特点,ER-α36介导的信号通路及ER-α36在乳腺癌治疗中的作用研究进展.

米非司酮下调不全流产患者蜕膜雌激素受体(ER)及孕激素受体(PR)表达

目的了解不同剂量米非司酮对人工流产术后不全流产残留物中绒毛膜促性腺激素-β(β-human chorionic gonadotrophin,β-hCG)及雌激素受体(estrogen receptor,ER)、孕激素受体(progesterone receptor,PR)表达的影响。方法 60例2009年1至9月自愿在复旦大学附属妇产科医院计划生育门诊就诊的早孕人工流产术后不全流产妇女,随机分为4组:A、B、C组术前分别服用米非司酮1 400 mg(100mg,bid×7d)、700 mg(50mg,bid×7d)、350 mg(25 mg,bid×7d),D组为对照组,每组各1 5例。除D组直接行清宫术,其他组于停药后行清宫术。应用免疫组织化学EnVision法染色,半定量测定残留物中β-hCG及ER、PR水平。结果 4组β-hCG在绒毛滋养叶细胞胞质的表达差异无统计学意义(P>0.05)。ER、PR在蜕膜上皮细胞和间质细胞核中的表达,实验组较对照组表达均降低,差异均有统计学意义(P<0.05)。经两两秩和检验(修正α=0.05):ER在蜕膜上皮细胞核中的表达为A组较C、D组明显降低,差异有统计学意义(P<0.05);ER在蜕膜间质细胞核中的表达为A组较其他组明显降低,差异有统计学意义(P<0.05);A、B、C组较D组表达降低,差异有统计学意义(P<0.05)。PR在蜕膜上皮细胞核中,A、B、C组较D组表达降低,差异有统计学意义(P<0.05)。PR在蜕膜间质细胞核中的表达A组较其他组表达明显降低,差异有统计学意义(P<0.05);B组较C、D组表达降低,差异有统计学意义(P<0.05)。结论不同剂量的米非司酮对人工流产术后不全流产残留物中β-hCG的表达影响不明显。对蜕膜细胞中的ER、PR表达有抑制作用,此抑制作用可能是米非司酮治疗不全流产的作用机制之一。1 400 mg米非司酮治疗效果最显著。

ER和PRmRNAs在内异症子宫内膜表达的变化

目的 :探讨雌激素受体 (ER)和孕激素受体 (PR)在子宫内膜异位症 (内异症 )子宫内膜的表达。方法 :利用大鼠内异症动物模型 ,采用逆转录聚合酶链反应 (RT PCR)技术 ,检测子宫内膜ER和PRmRNAs的表达情况。结果 :内异症模型组大鼠异位内膜ER、PRmRNAs的表达低于在位内膜和对照组正常子宫内膜 ,与后两者比较差异有显著性意义 (P <0 .0 1) ;而模型组在位内膜ER、PRmRNAs的表达与正常对照组比较差异无显著性意义 (P >0 .0 5 )。内异症模型组异位内膜ER/PRmRNA比值大于在位内膜和正常子宫内膜ER/PRmRNA比值 (P <0 .0 1)。结论 :内异症大鼠异位内膜ERmRNA表达的相对增高在内异症的发生与发展中起着一定的作用。