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.
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.
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.
Objective To explore the role of estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) in estrogen-induced proliferation of endometrial cancer, and explore whether metformin inhibits the proliferation of endometrial cancer cells through ERα and ERβ. Methods Stable transfected Ishikawa cells were constructed by lentivirus. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were detected by methyl thiazolyl tetrazolium assay. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell cycle were detected by flow cytometry. In addition, quantitative real-time polymerase chain reaction and Western blotting assays were used to detect changes in the expression of cyclinD1 and P21 involved in cell cycle regulation. The effects of down-regulated ERα and ERβ on estrogen-induced Ishikawa cell proliferation were observed by adding metformin to estrogen treatment. Results Down-regulation of ERα inhibited the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERα also inhibited the expression of cyclinD1 and promoted the expression of P21 (P<0.05). Down-regulation of ERα counteracted the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Down-regulation of ERβ promoted the proliferation and cell cycle of Ishikawa cells (P<0.05). Down-regulation of ERβ also promoted the expression of cyclinD1 and inhibited the expression of P21 (P<0.05). Down-regulation of ERβ enhanced the effect of estrogen-induced cell proliferation, cell cycle, and the expression changes of cyclinD1 and P21 (P<0.05). Metformin inhibited the proliferation of estrogen-induced Ishikawa cells (P<0.05), while in the down-regulated ERα Ishikawa cells or down-regulated ERβ Ishikawa cells, the inhibition of metformin on Ishikawa cells disappeared (P<0.05). Conclusions ERα may promote estrogen-induced proliferation of endometrial cancer cells, while ERβ may inhibit estrogen-induced proliferation of endometrial cancer cells. In addition, ERα and ERβ may also mediate the inhibitory effect of metformin on endometrial cancer cells.
ObjectiveTo detect protein expression of androgen receptor (AR) in patients with estrogen receptor (ER)-positive primary breast cancer and investigate its significances on prognosis.MethodsThe clinicopathologic data of female patients with ER-positive primary breast cancer in the Affiliated Hospital of Southwest Medical University from January 2012 to December 2012 were retrospectively analyzed. The AR protein expression in the breast cancer tissue was detected by the immunohistochemistry. The relationship between the AR protein expression and the clinicopathologic characteristics such as the age, tumor diameter, invasive biological behavior, molecular typing or the survival after the operation was analyzed.ResultsThe positive rate of AR protein expression was 58.5% (76/130) in the patients with ER-positive primary breast cancer. The positive rates of AR protein expression in the patients with the low differentiation, clinical stage Ⅲ+Ⅳ, p53 positive, neurovascular invasion, and lymph node metastasis were significantly lower than those in the patients with the moderate and high differentiations, clinical stage Ⅰ +Ⅱ, p53 negative, without neurovascular invasion, and without lymph node metastasis (P<0.050). The positive rate of AR protein expression was not correlated with the age, menstrual status, tumor diameter, progesterone receptor and Her-2 statuses, Ki-67, or molecular typing (P>0.050). The 3-year and 5-year overall survival and tumor-free survival of the AR-positive patients were significantly higher than those of the AR-negative patients (P<0.050). The 5-year cumulative total survival and tumor-free survival of the AR-positive patients were significantly better than those of the AR-negative patients (χ2=8.134, P=0.004; χ2=9.150, P=0.002).ConclusionsPatient with AR protein positive expression in ER-positive breast cancer has a better differentiation, lower clinical stage, and weaker invasiveness. Long-term survival of patient with AR protein positive expression after standardized treatment is also better than that of patient with AR protein negative expression. It might provide an important additional information on prognosis and become a promising object for targeted therapy.
ObjectiveTo explore expression of Mdm2 in the estrogen receptor α (ERα)-positive breast cancer tissues and fibroadenoma of breast tissues, and to explore the effect of MDM2-siRNA on cell proliferation, colony formation, and apoptosis for MCF-7 cells. Methods① Seventy eight ERα-positive breast cancer patients identified by histopathological examination, who underwent surgery in our hospital from June 2012 to October 2015, as well as 10 fibroadenoma of breast patients underwent surgery in the same period, were collected retrospectively to determine the expression of Mdm2, then explore the relationship between the expression of Mdm2 and clinical pathological characteristics of ERα-positive breast cancer patients. ② MCF-7 cells were divided to MDM2-siRNA group (added with MDM2-siRNA), negative control group (added with negative siRNA), and blank control group (added without any reagent). Expression of Mdm2, cell proliferation rate, number of colony formation, and apoptosis rate were determined in the MCF-7 cells of 3 groups. Results① No one of fibroadenoma of breast patients was found positive expression of Mdm2 (0/10), and 38 of 78 ERα-positive breast cancer patients were found the positive expression of Mdm2 (48.7%), which is higher than that of fibroadenoma of breast tissues (χ2=12.357, P=0.000). In ERα-positive breast cancer patients, expression of Mdm2 was related with TNM staging and number of metastasic lymph node (P < 0.050), the positive expression rate of Mdm2 was higher in patients with later TNM staging or more metastasic lymph node. ② Cell proliferation rates on 2, 3, and 4 days after transfection, expression level of Mdm2, and number of colony formation were all lower (P < 0.050), but the apoptosis rate was higher in MDM2-siRNA group (P < 0.050), comparing with negative control group and blank control group. But there was no significant difference between negative control group and blank control group on aforementioned indexes (P > 0.050). ConclusionMdm2 is a diagnostic marker in ERα-positive breast cancer patients, and treatment targeting it might has a certain therapeutic value.
Objective To study the effects of estrogen and progesterone and their receptors on the development of gallstone (GS) and primary gallbladder carcinoma (PGC), and probe to the relationship between the biological characteristic of PGC and female hormone and their receptors. Methods The study of PGC related to female hormone was reviewed by history document and experimental study in resently. Results The female hormone influenced human body extensively: they acted on not only the target organs, but also the nontarget organs with their receptors. The action was brought about by their receptors expression. The action intensity was dependent on not only the serum level of female hormone but also their corresponding receptors distributing in organs. The carcinogenic mechanism of estrogen was more clear with the discovery of estrogen-regulating-proteins. Conclusion The estrogen play an important role in the onset and development of GS and PGC. Estrogen and progestrone can inhance the patients′ susceptibility to the cholesterol gallstone and become a high risk factor in causing PGC through inducing their corresponding receptors expression in the gallbladder. Evaluating the effects of estrogen-estrogen receptor-estrogen-regulating-protein on biological characteristic of PGC is significant in guiding clinical endocrine treatment.
ObjectiveTo investigate the relationship between the polymorphisms of estrogen receptor α (ERα) gene PvuⅡ, XbaⅠ and breast hyperplasia. MethodsPolymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of ERα gene PvuⅡ, XbaⅠ in breast hyperplasia patients (study group, n=89) and healthy controls (control group, n=35). ResultsThe differences of the genotypic frequency and allele frequency of the ERα gene Xba Ⅰ were significant between the study group and the control group (Plt;0.05). According to analysis of the odds ratio (OR), the risk of developing breast hyperplasia for X allele carriers was 0.551 as compared with x allele carriers. But there was no significant difference for the gene polymorphism of PvuⅡ between the study group and the control group (Pgt;0.05). ConclusionThe polymorphisms of XbaⅠof ERα gene is associated with breast hyperplasia and the mutant gene increases breast hyperplasia risk.