The Role Of N-Myc Downstream Regulated Gene 1 On Carcinogenesis Of Endometrioid Adenocarcinoma

Tumorigenesis is the result of multiple factors which implicate in destruction of balance between oncogene and anti-oncogene. PTEN (phosphatase and tensin homology deleted on chromosome ten) has been ascertained to be an anti-oncogene whose alteration can enhance multiple tumor-related genes by up-regulating HIF-1(hypoxia-inducible transcription factor-1) in carcinogenesis. NDRG1 (N-Myc downstream regulated gene 1) overexpression was reported in prostate, breast and colon cancers. In hypoxic conditions, NDRG1 was implicated in tumorigenesis and metastasis by inducing cell's transformation to facilitate the cell's survival. Last year, researchers used Ishikawa endometrial carcinoma cells to verify that Estrogen-ER complex involved in endometrial carcinogenesis through ER-dependent PI3K/AKT pathway.Therefore, we supposed that (1) whether NDRG1 expresses higher in endometrioid carcinoma as it does in prostate, breast and colon cancer? (2) whether PTEN loss/mutation and NDRG1 expression are related to each other in endometrioid carcinoma? (3) whether PTEN alteration,HIF-1 and NDRG1 expression are related in the ischemic area in the endometrioid carcinoma? and (4) whether other pathway beside PTEN-PI3K/AKT-NDRG1 pathway such as estrogen related endometrial carcinogenesis is correlated with NDRG1?Firstly, we verified that NDRG1 expressed higher in endometrioid carcinoma than that in normal endometrium both at protein and at mRNA level by using immunohistochemistry, in situ hybridization and RT-PCR method just as in prostate, breast and colon cancer. We suggested that NDRG1 is a tumor-related gene whose overexpression is closely related to endometrial carcinogenesis and progression.Secondly, we ascertained that PTEN alteration and NDRG1 expression were increasing during the process from normal endometrium to atypical hyperplasia and endometrioid carcinoma. Their expressions were correlated with each other in endometrioid carcinoma. We suggested that PTEN alteration may upregulate NDRG1 during the process of endometrial carcinogenesis.Thirdly, we found higher expression of PTEN alteration, HIF-1 and NDRG1 in the ischemic area in the endometrioid carcinoma. Their expressions were related to one another in the ischemic area. We suggested that PTEN alteration enhanced NDRG1 by up-regulating HIF-1 to implicate in endometrial carcinogenesis and progression.At last, we found ERa expression was decreasing from normal endometrium to atypical hyperplasia and endometrioid carcinoma. ERa and NDRG1 expressions were negatively correlated. We suggested that NDRG1 involved in estrogen related endometrial carcinogenesis together with ERa.