N-myc downstream-regulated gene 1 as a downregulated target gene of PTEN in the controlling of tumourigenesis in endometrioid carcinoma.

ABSTRACT

BACKGROUND & OBJECTIVE: Mutation/deletion of PTEN has been known to be involved in the development of many cancers including endometrial carcinoma. NDRG1 (N-myc downstream-regulated gene 1) is reported to be associated with tumourigenesis. PTEN expression has been shown to be correlated with NDRG1 in both prostate and breast cancer. In this study, we explored the possibility that PTEN alteration may cause carcinogenesis of endometrioid carcinoma by regulating the expression of the NDRG1 gene. METHODS: Tissue blocks of 103 patients with pathologically confirmed endometrioid carcinoma were included. All the carcinoma tissues were accompanied with varied degree of necrosis. Using two-step method and avidin-biotin peroxidase complex immunohistochemistry method, the correlation of the two genes expression in ischaemic area and the relationship of NDRG1 expression between ischaemic and non-ischaemic area in endometrioid carcinomas was evaluated. RESULTS: PTEN alteration and NDRG1 expressions were significantly increased in the ischaemic area of endometrioid carcinoma compared with their expressions in the normal endometrium respectively (P<0.001, P<0.001). A positive correlation was found between PTEN alteration and NDRG1 expression in the ischaemic area of endometrioid carcinoma. INTERPRETATION & CONCLUSION: We suggest that NDRG1 may be an important candidate gene in facilitating endometrium carcinogenesis in the adaptation of hypoxia for survival. Alteration of PTEN may upregulate NDRG1 expression, which plays an important role in the process leading to endometrial carcinogenesis.