The Effect Of POGLUT1 In Combination With Notch1 Signaling Pathway To The Malignant Degree Of Endometrial Carcinoma

Background Endometrial carcinoma is one of the three most common gynecological malignancies, accounting for 20–30% of all female genital tract cancers,the mortality in all female malignant tumor is seventh.Patients with early stage Endometrial carcinoma is treated by surgical procedures,afer surgical treatment can choose radiotherapy or chemotherapy according to risk factors.Patients with advanced or recurrent mainly adopt combination radiotherapy-chemotherapy.In recent years, the disease shows an increasi-ng morbidity worldwide,but its pathogenesis is still not clear.Therefore,it is urgent and necessary to explore its pathogenesis and altemative therapeutic approaches to overcome this aggressive disease.The Notch signaling pathway is a pivotal mechanism during early development and in adult organisms affecting basic processes like differentiation, proliferation, and apoptosis.The deregulation of Notch signalling leads to several pathological conditions, including cancer.Expression and localizalion of Notch receptors and their ligands have been observed in the endometrium tissue and altered during endometrium tumorigenesis. So this pathway may be critical for the abnonnal tumorigenesis.Protein O-glucosyltransferase(POGLUT1) can modify extracellular dom ain of Notch receptors,is of great significant to the biological char acteristics of Notch receptors.Researches show that,knockdown of POGL UT1 resulted in decreased protein levels of endogenous Notch1, Notch intracellular domain(NICD),and Notch target gene Hes-1, suggesting t he impairment of the Notch signaling. In addition, down-regulated exp ression of POGLUT1 inhibited the proliferation of cells.Therefore,we Hypotheses POGLUT1 combine Notch signaling pathway can promote the oc-ccurrence and development of endometrial carcinoma.In this study,the expression and the biological significance of POG LUT1 and Notch signaling pathway in endometrial carcinoma were examin ed,which might lay the new theoretical foundation for clinical diagno-sis and treatment in endometrial carcinoma.Methods The expression of ER、PR、POGLUT1、Notch1、CBF1and HESl were studie d in 9 cases of type I endometrial carcinomas,6 cases of type II end ometrial carcinomas and 6 cases of normal endometrium tissue by immun-ohistochemical staining.Data are presented as mean ± SE where appli cable. Differences were evaluated using Student’s t-tests. P values< 0.05 were considered statistically significant.Results1.Estrogen receptor(ER)、Progesterone receptor(PR) in type I endome trial carcinoma were high expression, in type II endometrial carcinom a donot express or weak expression.2.The positive expression rates of POGLUT1、Notch1、CBF1、HES1 in endometrial carcinoma were all significantly higher than that in the normal endometrium tissue(P<0.05).3.The positive expression rates of POGLUT1、Notch1、CBF1、HES1 in type I endometrial carcinoma and type II endometrial carcinoma were all significantly higher than that in the normal endometrium tissue(P<0.05,P<0.01).4.The positive expression rates of POGLUT1、Notch1、CBF1、HES1 in type II endometrial carcinoma were all significantly higher than th at in the type I endometrial carcinoma(P<0.05).5.The expression of POGLUT1、Notch1 had no relevant with histologic al grade and clinical staging(P<0.05).Conclusion1.The positive expression rates of Notch1 in endometrial carcinoma were all significantly higher than that in thenormal endometrium tis sue.This supports the notion that Notch pathway can function as oncog-enic in human endometrial cancer.2.The positive expression rates of POGLUT1、Notch1、CBF1、HES1 in endometrial carcinoma were all significantly higher than that in the normal endometrium tissue.It showed that POGLUT1 can activated Notch signaling pathway to promote the occurence and development of endomet-rial carcinoma.3.The positive expression rates of POGLUT1、Notch1、CBF1、HES1 in type I endometrial carcinoma and type II endometrial carcinoma were all significantly higher than that in the normal endometrium tissue.And they in type II endometrial carcinoma were all significantly hig her than that in the type I endometrial carcinoma.It prompted that PO-GLUT1 in combination with Notch signaling pathway associated with th-e pathological type of endometrial cancer.