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Primary biliary cholangitis (PBC) is a chronic, non-suppurative, autoimmune cholestatic group of liver disorder, which more frequently affects middle-aged women and eventually leads to liver failure. Its pathogenesis is not completely clear, yet the study has confirmed that the occurrence and development of PBC is closely associated to the individual's genetic background, with obvious genetic heterogeneity. Currently, PBC has been divided into five types based on their related genes dissimilarities, aside from PBC-1, which is an autosomal dominant inheritance, while the other four types of inheritance are unidentified. The ratio of middle-aged women to male cases with PBC goes overs 9:1, and it mostly occurs in perimenopausal period. It is speculated that the occurrence of PBC may be related to estrogen and estrogen receptors. This article reviews the advances in the study of genetic theory of PBC and the role of estrogen and its receptor in this disease.
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Objective To investigate the changes aad possible role of estrogen and its receptor ERα、ERβ、GPR30 in the pathogenesis of asymptomatic hyperuricemia.Methods The peripheral blood of 62 asymptomatic hyperuricemia patients (AH) and 68 healthy controls (HC) were collected.The expression of estradial (E2) in serum was detected by the chemilluminescent microparticle immunoassay (CMIA).The expression of ERα,ERβ,GPR30 mRNA in peripheral blood mononuclear cells (PBMCs) was measured using Real time quantitative polymerase chain reaction (RT-qPCR).Statistical Package form Soci-science (SPSS) 17.0 statistical software was used for data analysis.The measurement data were compared by t test,rank sum test or one factor analysis of variance test.The correlation between variables was used by Spearman correlation analysis.Results ① The expression of E2 in serum of the HC group was higher than that in the AH group [(38.7±10.2) pg/ml vs (33.7±8.6) pg/ml,Z=-0.356,P＜0.05].② The expression of ERα,GPR30 mRNA in PBMCs of HC group was increased,compared with that in the AH group (0.000 17±0.000 23 vs 0.000 12± 0.000 12,0.002 0±0.002 1 vs 0.001 5±0.000 8,Z=-2.112,-2.147,P＜0.05,respectively).No significant difference in PBMCs ERβ mRNA levels was found between HC group and AH group,while a slight but not significant increase was observed in HC group.③ The Spearman correlation analysis found that the expression of ERα and ERβ mRNA,E2 and GR,ERβ and GLU in the AH group were positively related (r=0.259,0.251,0.260,P＜0.05,respectively).Conclusion The expression of E2,ERα,ERβ,GPR30 mRNA in the peripheral blood of patients with AH is decreased,suggesting that the estrogen and its receptor may be involved in the patho-genesis of hyperuricemia.
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Objective To observe the expression of estrogen receptors (ERαand ERβ) on gastric cancer cells and evaluate the effect of Tamoxifen(TAM) on the cell proliferation and expression of serine proteinase inhibitor 9(PI9) of gastric cancer cells . Methods PI9 positive expression(MNK45 ,SGC7901)and negative expression (BGC823)of gastric cancer cell lines were from pre‐liminary screened ,the expression of ERα and ERβ detected by immunofluorescence chemical method ,the cell proliferation and ex‐pression of PI9 were tested by CCK8 assay and reverse transcription‐PCR after intervention of TAM .Results ERαprotein expres‐sion was noted in MNK45 and SGC7901 ,ERβwas noted in BGC823 ,but the expression of ERαand ERβwere not appear to be obvi‐ous after the intervention of TAM .Tamoxifen could obviously inhibited cell proliferation of MNK45 and SGC7901 at concentration of 0 .1-100 .0 μmol/L ,the differences were statistically significant compared with negative control group (P<0 .05) ,but showed no dose‐dependent to the proliferation of BGC823 and MNK28 .After treating with TAM ,the expression of PI9 mRNA of SGC7901 (0 .402± 0 .020) and MNK45(0 .359 ± 0 .048) were obviously lower than that in the negatwe control group(P< 0 .05). Conclusion Tamoxifen could significantly inhibit the proliferation of PI9 positive expression than PI9 negative expression of gastric cancer cell lines ,and showed obviously dose‐dependent ,its role in inhibiting proliferation might closely related to immune tolerance improved by PI9 .
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Objective To characterize the expressions of androgen receptor (AR) and estrogen receptor (ER) in penis skin of patients with congenital hypospadias. Methods Dorsal prepuce, ventral prepuce, and urethral plate were harvested from 30 patients with congenital hypospadias. The expressions of AR and ER in epidermal cells and dermal fibroblasts were assessed respectively by automated immunohistochemistry. Image Pro plus 6.0 was used to analyze the optical density (OD) value of AR and ER in different parts of epidermal cells and dermal fibroblasts. Results AR and ER were located mainly in nucleis of the squamous basal cells and prickle cells, and were also found in nucleis of subcutaneous fibroblast cells. The expression of AR was lower in epidermis of urethral plate than that of dorsal prepuce and ventral prepuce (P<0.05), but no significant difference was detected in dermal fibroblasts. The expression of ER was higher in epidermis of dorsal prepuce than that of urethral plate and ventral prepuce (P<0.05). The dermal expression of ER in fibroblast cells was increased successively in dorsal prepuce, ventral prepuce and urethral plate (P<0.05). Conclusion Lower expression of AR in urethral plate may contribute the development of hypospadias. Disorder of ER in dermal fibroblast cells of prepuce may play an important role in hypospadias.
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Objective To observe the different expressions of androgen and estrogen receptor in nucleus membrane of human prostate stromal cells under anoxic or normoxic conditions.Methods Human prostate stromal cell line WPMY-1 was cultured in vitro.At 4,8,12,24,48 h after cellswere seeded,the mRNA and protein expression of androgen receptor (AR) and estrogen receptor (ER) in prostate stromal cells were tested by RT-PCR and immunohistochemistry method,respectively.Results The exprcssions of AR and ER were significantly increased in prostate stromal cells under anoxic conditions compared with under normoxic conditions.The relative expression of AR mRNA was 0.35±0.01 in anoxic prostate stromal cells at 4 h,and increased to 1.40±0.02 at 48 h,which was higher than in normoxic prostate epithelial cells [0.27 ± 0.01 and0.36± 0.01] synchronously (t=28.182,both P ＜ 0.001).Immunohistochemistry showed significantly increased AR-positive cells under anoxic conditions as compared with under-normoxiccondition from 12 h synchronously [(33.72±4.19) per 200 cells,(23.84±1.31) per 200 cells,t=3.902,P=0.018].The expression of ER mRNA was 0.39±0.01 in prostate stromal cells at 4 h,and increased to 0.59±0.01 at 48 h under anoxic conditions,which were higher than under normoxic conditions (0.31±0.01 and 0.46±0.13) synchronously (both P＜0.001).Immunohistochemistry showed the significantly increased ER-positive cells under anoxic conditions as compared with under normoxic condition from 4 h to 48 h synchronously [(13.42±0.80) per 200 cells and (55.16±0.41) per 200 cells； (9.68±0.63) per 200 cells and (22.95±0.55) per 200 cells,t=81.130,P＜0.001].Conclusions The expression of androgen and estrogen receptors is upregulated in human prostatestromal cells under anoxic conditions.
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ObjectiveTo investigate the expression of estrogen receptor(ER)and progesterone receptor(PR)in intrahepatic cholangiocarcinoma(ICCA)and extrahepatic cholangiocarcinoma(ECCA)comparatively.MethodsThe expression of ER and PR was detected in 24 specimens of ICCA and 34specimens of ECCA by immunohistochemistry assay.ResultsThe positive rates for ER and PR expression were 29 ％(7/24)and 46 ％(11/24)in ICCA specimens,respectively.3 cases among 9 cases of high histological grade,3 cases among 11 cases of middle histological grade and 1 case among 4 cases of low histological grade expressed ER positively,while 2 cases,7 cases and 2 cases expressed PR positively,respectively.The expression of ER and PR expressions showed no statistically significant differences between different histological grades of ICCA.ER and PR were all negative in 34 specimens of ECCA.Conclusion ER and PR show significant different expression between ICCA and ECCA,with exclusive positive expression in ICCA.ER and PR might be involved in the pathogeuesis of ICCA.
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Frequentes deleções e mutações têm sido descritas no gene p16 em diversos tipos de tumores, mas pouco se sabe sobre o valor preditivo do p16 na hormonioresistência ao tratamento do câncer de mama. Objetivos: Estudar a expressão do p16 e dos receptores de estrogênio e progesterona (RE e RP) em pacientes com carcinoma de mama RE e/ ou RP (+) após curto período (26 dias) de tratamento com tamoxifeno, anastrozol e placebo. Métodos: Estudo prospectivo randomizado duplo-cego realizado com 58 pacientes na pós-menopausa diagnosticadas com carcinoma ductal invasivo de mama nos estádios II e III, que no período pré-operatório foram subdivididas em três grupos: P (placebo, n = 25), T (tamoxifeno 20 mg/dia, n = 15) e A (anastrozol 1 mg/dia, n = 18). A biópsia foi realizada no momento do diagnóstico e após a cirurgia definitiva (26° dia). Realizou-se o estudo semiquantitativo utilizando-se os critérios de Allred. Resultados: A positividade do p16 variou de 22 para 17%, respectivamente no pré e no pós-tratamento com anastrozol; variou de 8 para 4% no grupo placebo e não houve variação, com 7% de positividade no grupo que recebeu tamoxifeno. A comparação entre grupos e tempos não apresentou relação significativa para o p16 (p = 0,17). Não foi encontrada correlação entre a positividade do p16 e o status hormonal (RE e RP). Conclusão: Não houve diferença estatística significativa entre os três grupos estudados. Outros biomarcadores deverão ser pesquisados para se identificar precocemente a hormônio-resistência e a especificidade terapêutica.
Common deletions and mutations have been described in the p16 gene in various tumor types, but little is known about the predictive value of p16 in hormonioresistência the treatment of breast cancer. Objectives: To study the expression of p16 and estrogen receptor and progesterone (ER and PR) in patients with breast carcinoma ER and / or PR (+) after a short period (26 days) of treatment with tamoxifen, anastrozole and placebo. Methods: A prospective randomized double-blind study conducted with 58 postmenopausal patients diagnosed with invasive ductal breast carcinoma in stages II and III than in preoperative period were divided into three groups: P (placebo, n = 25) T (tamoxifen 20 mg / day, n = 15) and A (anastrozole 1 mg / day, n = 18). A biopsy was performed at diagnosis and after definitive surgery (26 days). We carried out the study using semiquantitative criteria Allred. Results: The positivity of p16 ranged from 22 to 17%, respectively, before and after treatment with anastrozole; ranged from 8 to 4% in the placebo group and no variation, with 7% positivity in the group receiving tamoxifen. The comparison between groups and time showed no significant relationship to the p16 (p = 0.17). No correlation was found between the positivity of p16 and hormonal status (ER and PR). Conclusion: There was no statistically significant difference among the three groups. Other biomarkers should be investigated for the early identification of resistance to hormone therapy and specificity.
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Humans , Female , Carcinoma, Ductal, Breast , /physiology , Breast Neoplasms/therapy , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Immunohistochemistry , Aromatase Inhibitors , Postmenopause , Tamoxifen/therapeutic use , Neoadjuvant TherapyABSTRACT
Objective To investigate the effects of different doses of estradiol on apoptosis of T lymphocytes from spleens in ovariectomized mice and explore the possible mechanisms.Methods The mice splenic T lymphocytes were isolated and divided into ten groups: young group, sham- ovariectomized group, ovariectomized group, ovariectomized plus estradiol(10-11, 10-10, 10-8 and 106groups, ovariectomized plus estradiol (10-10mol/L) plus 1CI182 780 (10-7tool/L) group, ovariectomized plus estradiol(10-10mol/L) plus 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPP, 10-6mol/L) group, ovariectomized plus estradiol(10-10mol/L) plus pyrroline dithiocarbamate(PDTC, 10-6mol/L) group. The apoptosis rates were determined by flow eytometry using Annexin V-FITC/ PI and the protein levels of ERa, ERβ, Bax, Bcl-2 and P65 were detected by Western blot. Results The apoptosis rate of ovariectomized group was(19. 4±2.5)%, which was higher than that of young group [(14.6±2.4%) 3 and sham-ovariectomized group [p (14.5±2.3)%], and the levels of Bcl-2 and nuclear P65 were lower than the young group [(0. 25±0. 05, 0. 09±0. 01) vs. (0. 40± 0.07,0. 15±0. 02), P<0.01]. The ovariectomized plus estradiol (10-10tool/L) group had lower apoptosis rate and higher Bcl-2 and P65 levels compared to the ovariectornized group[(16.6±1.8)% vs.(19.4±2.5)%,P<0.05;0.36±0.03 vs. 0.25～0.05, 0.14±0.01 vs. 0.09±0.01, P< 0. 01)], while the ovariectomized plus estradiol(10-8mol/L, 10-6tool/L) groups had higher apoptosis rates than the ovariectomized group[(22. 55±2. 5)% vs. (19. 4±2. 5)% ,P<0. 05;(27.8±3.1)% vs. (19.4 4±2. 5)%,P<0. 01, respectively]. The 2protein levels of ERa and ERβ of ovariectomized group were 0. 23±k0.01 and 0. 22±0. 03, respectively, which were lower than those of young((0. 27±0. 02) and (0. 29±0.04)] and sham-ovariectomized group [(0. 28±0. 03) and (0. 29±0.02)]. The ovariectomized plus estradiol(10-1110-1010-8tool/L) groups had higher while ovariectomized plus estradiol(10-6mol/L) group had lower ERα and ERβ protein levels (0. 09±0. 01,0. 14±0.02) than the ovariectomized group(P<0. 01). There was no significant difference between ovariectomized plus estradiol(10-10mol/L) plus ICI182 780 group or ovariectomized plus estradiol(10-10tool/L) plus PDTC group and ovariectomized group [(19.4±1.6)% vs. (19.4±2. 5)%, (21.0±2. 9)% vs. (19.4d±2. 5)%, P>0. 05). There were also no significant difference between ovariectomized plus estradiol(10-10mol/L) plus MPP group and ovariectomized plus estradiol (10-10mol/L) grou p[(16.9±2.2)% vs. (16.6±1.8)%, P>0.05]. Conclusions The ovariectomy of mice leads to increased apoptosis rates of splenic T lymphocytes. The effects of estradiol on the apoptosis of T lymphocytes in ovariectomized mice are dependent on doses: physiological dose of estradiol inhibits while higher dose of estradiol exacerbats the apoptosis of T lymphocytes in ovariectomized mice.Physiological dose of estradiol may act on Rice T lymphocytes via ERβ and NFkB signaling.
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Objective To explore the effect of low-dose imfepristone on the endometrial simple hyperplasia.Methods Study group were randomly divided into two groups.43 cases in group mifepristone,43 cases in group norethindrone and control group were 20 cases.The endometrial histopathology and the contents of ER and PR were examined before and after the treatment.The changes of endometrial thickness and hemoglobin were detected,too.Results The endometria were all simple hyperplasia before taking the medicine and turned to proliferative stage after taking mifepristone and norethindrone.There were significant difference compared with taking the medicine before(P＜0.05).However,there were no statistical difference between two groups after taking the medicine(P＞0.05).The endometrial ER and PR were significantly depressed after taking the medicine compared with before in study group(P＜0.05).There were no significant difference between control group and group mifepristone after taking mifepristone(P＞0.05).But there were significant difference between controI group and group norethindrone after taking norethindrone(P＜0.05).The endometrum were significant turned thin and the contents of hemoglobin were significantly risen up after taking the medicine in study group(P＜0.05).But the contents of hemoglobin were significantly risen up after taking the medicine in group mifepristone compared with group norethindrone(P＜0.05).Conclusions Low-dose mifepristone can inhibit endometrial simple hyperplasia and turn the endometria from simple hyperplasia to proliferative stage.Low-dose mifepristone may adjust the endometrial ER and PR for inhibitting endometrial hyperplasia and make the expression of endometrial ER and PR decrease.But the contents of ER and PR were more close to normal after taking mifepristone.Low-dose mifepristone can attenuate the endometria and regain the hemoglobin fast.There are seldom side-effects after taking low-dose mifepristone.
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Objective: To investigate the effects of early exposure of new born rats to octylphenol (OP) on breast cancer incidence and breast cancer susceptibility gene 1 (BRCA1) expression. Methods: Female Sprague-Dawley rats were randomly divided into control (Con) group, model (Mod) group, OP 20, OP 40, OP 80 groups. OP was subcutaneously injected into rats from d 21 to d 27. The rats were given dimethylbenz[a]anthracene (DMBA) intragastrically on d 42 and were sacrificed on 180 d. The incidence of breast cancer, the changes in serum levels of estradiol and progesterone, the alteration of estrogen receptor (ER) expression and BRCA1 mRNA and protein expression in breast cancer tissues were observed. Results: No breast cancer occurred in Con group. The incidence rate of breast cancer in the Mod group, OP 20 group, OP 40 group, and OP 80 group were 70% (14/20), 60% (12/20), 25% (5/20), and 50% (10/20), respectively. The fluorescence intensities of BRCA1 expression were 31.54 ± 6.15, 36.27 ± 7.57, 61.69 ± 9.96 and 47.38 ± 10.45, respectively; the logarithm value of BRCA1 mRNA expressions were 3.46 ± 6.52, 4.12 ± 0.86, 5.53 ± 0.75, and 4.35 ± 0.58, respectively. The ER expression in breast cancer tissues decreased after the rats were exposed to OP. Conclusion: OP decreased the occurrence of DMBA-induced breast cancers, which may be related with up-regulation of BRCA1 expression and down-regulation of ER expression in breast cancers.
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Objective To observe the effect of Juli Sanjie Pill(JSP) on estrogen receptor(ER)? and ER? expression in the myometrium and hysteromyoma tissue,and to explore the correlation of ER? and ER? expression levels with the incidence of hysteromyoma. Methods Forty hysteromyoma patients were divided into two groups: 20 patients with operative indications after oral use of JSP and asking for operation,were enrolled in the treatment group,and other 20 patiens without mediation of medicine but asking for operation were in the control group.The ER? and ER? expression levels in hysteromyoma tissue and the surrounding normal myometrium of the two groups were detected by radioimmunoassay.Results There presented the expression of ER? and ER? in the hysteromyoma tissue and the surrounding normal myometrium of the two groups,and the levels in the hysteromyoma tissue were higher than that in the myometrium(P0.05).Conclusion The incidence of hysteromyoma is correlated with the local expression of ER? and ER? in the uterus.The therapeutic mechanism of JSP for hysteromyoma is probably related with the decrease of ER? and ER? expression levels in hysteromyoma tissue and with the decrease of ER? level in the surrounding normal myometrium.
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Objective:To study the effects of tamoxifen on proliferation and ER expression of human hepatocellular carcinoma cells.Methods:HepG2 cells were treated with tamoxifen at different concentration and different action time.MTT was used to determine the suppression rate of human hepatocellular carcinoma cell.The effects of tamoxifen on human hepatocellular carcinoma cell ER performance were observed by immunohistochemistry.Results:Tamoxifen inhibited the proliferation of human hepatocellular carcinoma cells and suppressed human hepatocellular carcinoma cell ER performence.Conclusions:Tamoxifen may suppress human hepatocellular carcinoma cell proliferation ER performance.
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Objective To investigate the function of estrogen in the proliferative and involuting stages of infantile hemangioma. Meothods Expression of estrogen receptor(ER),VEGF and bFGF were detected with SP immunohistochemical method in 42 cases of hemangiomas and 17 cases of vascular malformations.Results The label index(LI) of ER,VEGF and bFGF in the hemangioma was significantly higher than those in the vascular malformation and normal skin(P
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Objective To determine the relationship of ultrasonographic features and the expression of estrogen receptor(ER)in infiltrating duetal carcinoma(IDC)and infiltrating lobular carcinoma(ILC)of breast. Methods 118 patients with breast cancer were evaluated by ultrasonography.Ultra sonographic features in- cluded spiculate margin,posterior shadowing,microcalcifications,axillary lymphnodes metastasis,pre-and post-menopause and size of breast tumor.Scanning was performed before operation.The mastectomy speci- mens were stained with immunohistochemistry,and the expression of ER was measured.Results The expres- sion of ER was significantly correlated with spiculate margin and posterior shadowing in IDC and ILC(P0.05).Conclusion The biologic behavior and prognosis of breast IDC and ILC can be assessed according to ultrasonographic features to some extent.
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Estrogen receptor(ER),an important transcription factor belonging to the nuclear receptor superfamily,comprises two subtypes ER?and ER?.Estrogen receptor is expressed in prostate cancer and ladder cancer and has a compacted relationship with them.In this review,we summarized the structure,distri- bution,function of different estrogen receptor subtypes and progress in study on relationship between different estrogen receptor subtypes and prostate or bladder cancer.
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PURPOSE: To evaluate the relationship between the hormone receptor status, histologic grade and, the film-mammographic findings in primary breast cancer. MATERIALS AND METHODS: 198 breast cancer patients with hormonal receptor assay were included in this study. Estrogen receptor (ER) and progesterone receptor (PR) were determined by immunohistochemical method and enzyme-immunoassay. And film-mammographic findings were evaluated to disclose the relationship among the three variables (film-mmamographic findings, histologic grade and hormonal receptor status). Film- mammographic findings of the breast cancer are classified as spiculation, increased parenchymal density, calcification and mass. RESULTS: There is no correlation between estrogen receptor and histologic grade in 154 patients. Some correlation between estrogen receptor by enzyme-immunoassay and by immunohistochemistrical methods with 28 available data were observed (R=0.428). Among high estrogen receptor (ER) patients, there is a high possibility of spiculation or mass in mammography with 79 available data (Modified t-test, P<0.01). CONCLUSION: Spiculation or/and mass of the mammography can be related to the high possibile factor of the positive estrogen receptor or high level of estrogen receptor in primary breast cancer.
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Humans , Breast Neoplasms , Breast , Estrogens , Mammography , Receptors, ProgesteroneABSTRACT
Objective To study the expression of fascin, an actin bundling protein associated with cell motility, and the relationship with ER negative breast carcinoma.Methods Comparasion of the expression of fascin, estrogen receptor (ER) and proliferative cell nuclear antigen (PCNA) determined by immunohistological method was made on 84 specimens of primary breast carcinomas. Results The diffuse staining of fascin in cancerous cell cytoplasm was noted. Only 3 of 53 breast carcinomas with ER positive showed fascin positive expression (5.67%); in contrast, 21 of 31 carcinomas with ER-negative showed positive expression(67.7 %) (P
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Objective Whether changes of sexual hormones and sexual hormone receptors were involved in the pathogeny of chronic glomerulonephritis and uremia. Methods The maximal binding capacity (Bmax)' and dissociation constant (Kd) of androgen receptor (AR) and estrogen receptor (ER) in the peripheral leukocytes were estimated by radioligand binding assays in 63 patients with chronic glomerulonephritis and 101 with uremia. Results (1)The Bmax of AR was 638? 176, 508 ? 112 and 437? 126 sites/cell in men, child-bearing age womeru menopause women with chronic nephritis re-spectivily. The binding capacity was not different with controls. (2)The Bmax of ER was 1041?358, 1492 ? 387 and 1107 ? 274 sites/cell in three groups of chronic nephritis .respectively. They were all higher than those of controls ( P 1298? 413 and 10381284 sites/cell in three groups of uremia respectively. The binding capacity of ER was all higher than that of controls ( P
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The effect of 17?-estradiol ( 17?-E2 ) on expression of estrogen receptor ?( ER?) was observed in cultured MC63 cells and human osteoblast-like (HOB) cells. The results show that the expression of ER* is in a dose-dependent manner with 17p-E2 (0-1?10-6 mol/L) in MC63 cells and has an optimal 17?-E2 concentration (1?10-8 mol/L) in HOB cells resulting in maximum expression of ERp protein.
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The specific binding capacity of androgen receptor (AR)and estrogen receptor (ER)in the peripheral lymphocytes was estimated by radioligand binding assay in 130 diabetic patients (type Ⅰ 18 cases and type Ⅱ 112 cases). Results were as follows:1)plasma estradiol (E2) of diabetic patients was significantly lower than that of the controls (P