The Expression And Clinical Significance Of The New Estrogen Receptor GPR30 In Endometrial Cancer

Objective:Endometrial cancer is one of the three female malignant tumors. The mobidity has been rising up in these years. Many research has been demonstrate that endometrial cancer associates with the long-term stimulation of estrogen. Firstly, the estrogen binds with classical nuclear steroid estrogen receptors( ERα), and then mediates the transcriptional effects which in final play its biologic activity. We have found that there have been existed a rapid signal transduction and gene activiation after blocking up the classical estrogen receptor ERα. It hints that blocking ERαcan`t seal up estrogen receptor absolutely. Recent studies also demonstrate the existence of a 7-tansmembrane G protein-coupled receptors, GPR30 that responds to estrogen with rapid non-gennomic cellular signaling. The purpose of this investigation was to evaluate the expression of GPR30 mRNA, classical steroid estrogen receptor ERαmRNA, epidermal growth factor receptor EGFR mRNA and proto-oncogene c-fos mRNA, to probe the relationship between the clinical stage , the deep myometrial invasion and the histologic subtypes, and to research the pathogenesis that how the new estrogen receptor GPR30 and the classical estrogen receptor ERαlead to the development of endometrial cancer. Above all, according to this experiment we have known that GPR30 signaling is a critical pathway for tumor proliferation and progression, especially for typeⅡendometrial cancer. It was hoped to find a new stategy to guide the treatment and to assess the prognosis of endometrial cancer in clinic.Methods:1 The study subject:20 cases of endometrial cancer in the department of Gynecology and Planned Parenthood in the Second Hospital of Hebei Medical University were selected from September 2007 to November 2008. We selected the endometrium which had been diagnosed endometrial cancer in Pathology and had been operated. 10 cases of uterus sepyus which had have a examination of Hysteroscope were also seleced during the same period, and the endometrium of the uterus pepyus were also diagnosed through pathological methods. The clinical-operation stage of endometrial cancer of FIGO in 1988 was adopted in the research. All the patients had no hormone drug, no radiotherapy and no chemical medicine teatments during the past three months. All the patients had no gynecologic and obstetric diseases and other medical diseases. Diagnostic criterion for FIGO stages and sepyus pepyus was approved by Gynecology and Obstetrics written by Jie Yue.2 Tissues:With 20 minutes after operation of total hysterectomy and hysteroscope, human endometrium including the normal endometrium and abnormal endomotrial were obtained. These tissue samples of normal endometrium and carcinoma endometrium were taken from a total of three elective human endometrium. All the tissues were rinsed thoroughly in DEPC and immediately frozen in liquid nitrogen. Tissues were stored at -80℃until further analyses.3 The experiment methods:Reverse transcription polymerase chain reaction(RT-PCR) was employed for detection of the expression of GPR30 mRNA, ERαmRNA, EGFR mRNA and c-fos mRNA in normal endometrium and carcinoma endometrium; Analyze the relationship between the FIGO stages, myometrial invation, histologic subtypes and the expression of GPR30 mRNA, EGFR mRNA. All the values were expressed as mean±SD. Data were analyzed by the two-two comparison among the means of GPR30 mRNA, EGFR mRNA, ERαmRNA, c-fos mRNA by LSD-t method and correlation analysis between the means of GPR30 mRNA, EGFR mRNA. Statistical Product and Service Solutons 13.0(SPSS 13.0) was used to analyze the data. The level of significance was set at P<0.05.Results:1 The expression of GPR30 mRNA, ERαmRNA and EGFR mRNA was detected both in normal endometrium and endometrial carcinoma, and the c-fos mRNA was not detected in normal endometrium. The expression of GPR30 mRNA, EGFR mRNA and c-fos mRNA in endometrial carcinoma group were significantly higher than the expression in normal endometrium(P<0.05). No significant difference was found in the expression of ERαmRNA between normal endometrium and endometrial cancer.2 The expression levels of GPR30 mRNA in the tissues of myometrial invation exceeding and equal to 1/2 myometrium(7 samples) were significantly higher than those in the tissues of myometrial invation less than 1/2 myometrium(13 samples)(P<0.05); The expression levels of GPR30 mRNA, EGFR mRNA in the tissues of FIGOⅢ,Ⅳstages (9 samples)were significantly higher than those in the tissues of FIGOⅠ,Ⅱstages(11 samples)(P<0.05); And the GPR30 mRNA expression levels in the special histologic subtypes were significantly higher than whose expression in normal endometriums and adenocarcinoma endometriums (P<0.05). The special histologic subtypes include the 2 samples of uterine papillary serous carcinomas(USPCs), 2 samples of clear cell carcinoma and 1 sample of uterine undifferentiated carcinoma. 3 The expression levels of GPR30 mRNA and EGFR mRNA in the endometrial carcinoma tissues were positively correlated(r=0.507, P<0.05). No correlation between GPR30 mRNA and ERαmRNA was found in endometrial carcinomas(P>0.05); And no correlation was also found between EGFR mRNA and ERαmRNA (P>0.05).Conclutions:1 This research demonstrated that the expression levels of GPR30 mRNA, EGFR mRNA and c-fos mRNA in endometrial cancers were significantly higher than whose expression in normal endometriums. And the expression levels of GPR30 mRNA and EGFR mRNA were positively correlated. It illustrated that with the activation of EGFR, the new estrogen receptor GPR30 induce the break of oncogene c-fos, and finally leads to the endometrial cancer.2 There exists the close relationship between the expression of GPR30 and the prognosis of endometrial cancer. There will have worse concequences in endometrial cancer with higher expression of GPR30. And this research explained the possible cause for the endometrial carcinoma of special subtype.3 According to this research by blocking the new estrogen receptor GPR30 we can seal up the effect of estrogen absolutely, reduce the incidence rate of endometrial cancer, and improve the patients'survival. It will provide a new direction about the investigation of the prevention and cure of endometrial cancer.