InordertounderstandtherelationshipofP62CmycproteinexpressiontoERandPRinbreastcanceranditsclinicalsignificance,weexaminedexpressionofP62Cmycproteinin107breastcarcinomasbyusingimmunohistochemicaltechniques(LSAB).TheresultsshowedthatthepositiverateofP62Cmycproteinexpressionwas63.55%(68/107).TheoverexpressionofP62Cmycproteinrelatednegativelywithsurvival.94.00%ofthecaseswithoverexpressionofP62Cmycproteinsurvived≤5years,65.00%survivedgt;5yearslt;10yearsand21.62%survived≥10years.ThereweresignificantassociationsofP62Cmycproteinexpressionwithadvancedclinicalstage,highhistologicalgrade,andpositiveaxillarynodestatusinbreastcancer,butnorelationshipbetweenhormonereceptorsandP62Cmyc.AllofthesefindingssuggestthatoverexpressionofP62Cmycproteinmightbeanimportantprognosticfactor,andthedetectionofP62Cmycproteinmightbearrangedasaregularpathologicalexaminationinthecasesofbreastcancer.
ObjectiveTo explore the effects of exogenous estrogen receptor β1 (ERβ1) gene on the expression of human telomerase reverse transcriptase (hTERT) as well as the changes of proliferation ability in MDA-MB-231 cell line by transfecting recombinant eukaryotic expressing vector containing ERβ1 cDNA into human breast cancer MDA-MB-231 cell. MethodsRecombinant eukaryotic expressing vector containing ERβ1 cDNA was transfected into human breast cancer MDA-MB-231 cell by using cationic liposome as transfecting agent (acted as pcDNA3.1ERβ1 transfection group), empty vector group and non-transfection group acted as controls. The expression levels in both the mRNA and protein of both the ERβ1 and hTERT were tested by real-time PCR and Western blot, respectively. The change of proliferation ability in MDA-MB-231 cell was displayed by cell growth curve, and the change of cell apoptosis was detected by flow cytometry. ResultsThe expression level of ERβ1 mRNA in the pcDNA3.1-ERβ1 transfection group (0.449±0.077) significantly increased as compared with the nontransfection group (0.153±0.035) or the empty vector group (0.160±0.020), P=0.001 or P=0.000. The expression level of ERβ1 protein in the pcDNA3.1-ERβ1 transfection group (0.847±0.065) significantly increased as compared with the non-transfection group (0.356±0.050) or the empty vector group (0.390±0.030), P=0.001 or P=0.000. The expression level of hTERT mRNA in the pcDNA3.1-ERβ1 transfection group (0.127±0.020) significantly decreased as compared with the non-transfection group (0.283±0.025) or the empty vector group (0.283±0.049), P=0.001 or P=0.002. The expression level of hTERT protein in the pcDNA3.1-ERβ1 transfection group (0.147±0.023) significantly decreased as compared with the non-transfection group (0.783±0.025) or the empty vector group (0.802±0.019), P=0.001 or P=0.002. The rate of cell apoptosis in the pcDNA3.1-ERβ1 transfection group 〔(6.15±0.94)%〕 was higher than that in the non-transfection group 〔(1.41±0.42)%〕， P=0.001. Cell proliferation curve showed that proliferation ability significantly decreased in the pcDNA3.1-ERβ1 transfected groups as compared with the non-transfection group (Plt;0.05). ConclusionERβ1 could inhibit cell growth of human breast cancer MDA-MB-231 cell by down-regulating the expression of hTERT.
ObjectiveTo investigate whether Osteoglycin (OGN) gene inhibits the proliferation of Luminal breast cancer cells by up-regulating the expression of estrogen receptor (ER). Methods① Ualcan online database was used to analyze the expression of OGN in the breast cancer, and Kaplan-Meier Plotter was used to analyze the effect of OGN on the prognosis of patients with breast cancer. The median OGN mRNA expression level was taken as the cut-off point for high or low OGN expression. ② The expression of OGN mRNA in the Luminal breast cancer tissue of clinical case was examined using real time quantitative PCR (qRT-PCR). ③ Up-regulation of OGN expression in the Luminal breast cancer cell lines MCF-7 and T47D cells by transfection of overexpressing OGN plasmid, the expressions of OGN and ER were detected by qRT-PCR and Western blot, respectively. CCK8 assay and colony formation assay were applied to detect the cell proliferation and colony formation of Luminal breast cancer cells. ④ siRNA transfection was used to interfere with the expression of ER (ESR1) of breast cancer cells in the overexpressing OGN of breast cancer cells, then the CCK8 assay was used to detect the proliferation ability of the breast cancer cell lines after down-regulating the expression of ER in the overexpressing OGN patients. Results① The results of Ualcan online database showed that the expression of OGN mRNA in the breast cancer tissues of different types of breast cancer was lower than that in the normal breast tissues (P<0.001), and which was highest in the Luminal breast cancer tissues (P<0.001). The Kaplan-Meier Plotter prognosis analysis showed that in all breast cancer or Luminal breast cancer patients, the prognosis of patients with high OGN expression was better than those with low OGN expression (P=0.000 14, P=0.001 80). ② The OGN mRNA expression was decreased in the 30 Luminal breast cancer samples as compared with the corresponding adjacent normal breast tissues (t=4.774, P=0.000 019). ③ The expressions of OGN and ER in the MCF-7 and T47D cells were up-regulated after transfection of overexpressing OGN plasmid (P=0.000 002, P=0.000 001). The cell proliferation was inhibited (P<0.05) and the number of cell clones was decreased significantly (P<0.05). ④ After transient transfection of siRNA interfered with breast cancer cell lines of overexpressing OGN, ER mRNA level decreased (P<0.05), and cell proliferation ability increased significantly (P<0.05). Conclusion OGN could exert a tumor suppressor effect in Luminal breast cancer by mediating expression of ER.
Objective To explore the effect of toremifene on estrogen receptor （ER） expression and tumor micro-angiogenesis in rat Lewis lung carcinoma. Methods Cell suspension of rat Lewis lung carcinoma was implanted into 40 female Wistar rats subcutaneously. The rats were randomly divided into a control group，a estradiol group （0.006 mg/mL），a low dose toremifene group （0.25 mg/mL） and a high dose toremifene group （5 mg/mL）. Tumor size was measured every 3 days and the tumor growth curve was charted. On 15th day，the tumor weight and the growth inhibition rate were measured. Immunohistochemical method was used to detect the expressions of estrogen receptor α （ERα），estrogen receptor β （ERβ），vascular endothelial growth factor （VEGF），and platelet endothelial cell adhesion molecule-1 （PECAM-1）. Integral optical density （IOD） of ERα，ERβ and VEGF was calculated by image analysis software. Quantitative method of Weidner with PECAM-1 was employed for microvessel density （MVD） count. Results Tumor size of the four groups all presented a quadratic function growth trend with time （Plt;0.05）. Tumor growth speed was slower in toremifene groups of low and high doses than that in the control group and the estradiol group. The growth inhibition rate of the estradiol group，the low dose toremifene group and the high dose toremifene group was －15.1%，22.6%，and 45.1%，respectively. The expressions of ERα，VEGF，and MVD in the estradiol group were significantly higher than those in the control group，the low dose toremifene group and the high dose toremifene group （all Plt;0.05）. The expressions of ERα，VEGF，and MVD in the low dose toremifene group were significantly lower than those in control group，but higher than those in high dose toremifene group （all Plt;0.05）.The expression of ERα was positively related to VEGF （r=0.664，Plt;0.05） and MVD（r=0.593，Plt;0.05）. Conclusion Toremifene can inhibit tumor growth，which maybe involved in inhibiting ERα mediated VEGF expression.
The level of androgen receptor (AR), estrogen receptor (ER) and progesterone receptor (PR) of carcinoma and pericarcinoma tissue were determined in 30 cases of male hepatocellular carcinoma (HCC) patients operated by streptavidin peroxdase conjugated method, meanwhile used 20 patients with benign liver disease as a contrast group. The results showed that the positive rate of AR in tumor tisse was 80.0%, significantly higher than that in peritumor tissue (46.7%) and liver tissue of benign diseases (40.0%), Ｐ＜0.01, and there was no significantly difference between the latter two groups (Ｐ＞0.05). The positive rate of ER in carcinoma tissue (43.3%) was notably lower than that in pericarcinoma tissue (80.0%), Ｐ＜0.01. Statistically significantly difference wasn’t achieved in contrast with the benign diseases group (50.0%), Ｐ＞0.05. The positive rate of PR had no significantly difference among the three groups (Ｐ＞0.05). The authors suggest that sex hormone is related to initializing and developing of HCC by the action via its receptor, the level of AR and ER can be used as a prognosis determine index of HCC.
Biodistribution of125I-labeled 17α-vinyestradiol-3-acetate (125I-VE2A)in nude mice bearing human breast cancer containing different estrogen receptor (ER) content was studied to understand the relation between this compound and ER and, consequently, to develop the ER imaging. Each mouse was injected with 92.5 kBq tracer from tail vein and then killed after two hours. The radioactivity uptake rate in one gram of tumor tissue and tissues from other vital organs were measured, and the radioactivity uptake ratio of tumor to nontumor tissue was also measured. Results: The radioactivity uptake rate and the radioactivity uptake ratio of tumor to nontumor tissue in ER positive tumor (MCF-7) were much higher than those in ER negative tumor (MDA-MB-231). Conclusions: This compound, IVE2A has affinity to ER positive target organ or tumor and promise the probability to define the content and site of ER in vivo or in tumor.
ObjectiveTo explore the associations between estrogen receptor α (ESR1) gene intron 1 PvuⅡ (−397 T/C, rs2334693), XbaⅠ (−351 A/G, rs9340799) polymorphisms and premature ovarian failure (POF).MethodsLiterature published before February 2021 were retrieved in PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and CQVIP databases, according to the inclusion and exclusion criteria developed before. Odds ratio (OR) and 95% confidence interval (CI) were used for data analysis, the Q test and I2 statistic were used for heterogeneity analysis. Random-effect model or fixed-effect model was used according to I2 value. All analyses were performed by RevMan 5.3 software.ResultsSix case-control studies were included in this meta-analysis. For the associations between ESR1 gene intron 1 PvuⅡ polymorphisms and POF, there was no statistical difference in TT vs. CC model [OR=0.72, 95%CI (0.31, 1.70), P=0.46], TC vs. CC model [OR=1.09, 95%CI (0.83, 1.43), P=0.54], recessive model [OR=1.08, 95%CI (0.68, 1.70), P=0.74], or dominant model [OR=0.77, 95%CI (0.42, 1.42), P=0.41]. For the associations between ESR1 gene intron 1 XbaⅠ polymorphisms and POF, there was no statistical difference in AA vs. GG model [OR=0.88, 95%CI (0.44, 1.75), P=0.72], AG vs. GG model [OR=1.23, 95%CI (0.84, 1.79), P=0.29], recessive model [OR=1.14, 95%CI (0.81, 1.61), P=0.44], or dominant model [OR=0.75, 95%CI (0.41, 1.35), P=0.34], either. No statistical difference was found in the ethno-based subgroup analyses (P>0.05). Most models had obvious heterogeneities.ConclusionsCurrent evidence can’t confirm the associations between ESR1 gene PvuⅡ, XbaⅠ polymorphisms and POF. High-quality, multi-central and large-sample studies are still necessary to support this conclusion.
Objective To investigate the expressions of C-erbB-2, estrogen receptor (ER) and progesterone receptor (PR) in breast cancer tissues and to explore their relationship with patients-age, tumor size, lymph node metastasis, histopathological type and the stage of cancer. Methods The expressions of C-erbB-2, ER and PR in 83 cases of breast cancer tissues were detected by immunohistochemistry and the clinical significance was statistically analyzed. Results The positive expression rate of C-erbB-2, ER and PR in 83 cases of breast cancer tissues were 78.3%, 56.6% and 55.4%, respectively. The expressions of C-erbB-2, ER and PR were not correlated to patients’ age, tumor size, histopathological type and the stage of cancer (Pgt;0.05). While the expression of C-erbB-2 rather than ER and PR was correlated to lymph node metastasis (P＜0.05) and the correlation was positive (r=0.387, P＜0.05). Conclusion The positive expression of C-erbB-2 is one of lymph node metastasis factors for breast cancer patients. Combined detection of ER and PR expression may be helpful to clinical treatment and predict prognosis for breast cancer patients.
Objective To investigate expression of p16 protein in breast cancer and its clinical significance. Methods Using immunohistochemical techniques (LSAB) the expression of p16 protein in 107 breast carcinomas was examined. Results The positive rate of p16 protein expression was 40.19% (43/107). The p16 protein over expression of the cases surviving ≤5 years and surviving ≥10 years were 8.00% and 75.68% respectively. Conclusion Expression of p16 protein might play an important role in the prognosis of breast cancer.
ObjectiveTo investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice.MethodsEighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups (n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR).ResultsAll nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group (P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group (P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups (P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant (P<0.05).ConclusionThe level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.