Correlation between NDRG1 and PTEN expression in endometrial carcinoma

Abstract

N-myc Downstream-Regulated Gene 1 (NDRG1) is known as a differentiation-related gene that plays important roles in cell differentiation, organ formation, and embryonic development. NDRG1 has recently been shown to be associated with carcinogenesis and tumor progression in a wide variety of tumors. Phosphatase and tensin homolog deleted from chromosome (PTEN), a phosphatase and tensin homolog located on chromosome 10, is shown to be a tumor suppressor and is often mutated or deleted in various tumor cells, particularly in endometrial carcinoma. Using an immunohistochemical approach, we investigated the expression of NDRG1 and PTEN in normal endometrium, atypical hyperplasia, and endometrial carcinoma. All tumor tissues harvested in this study were derived from endometrioid carcinoma Type I, that were estrogenrelated. Our results demonstrate that the expression of NDRG1 was up-regulated in 5/40 (12.5%), 18/34 (52.94%), and 86/103 (83.5%) normal endometrium, atypical hyperplasia, and endometrial carcinoma cases, respectively (P < 0. The inactivation and mutation of tumor suppressor genes and the abnormal activation of proto-oncogenes may play important roles in the carcinogenesis and progression of endometrial carcinoma. N-myc Downstream-Regulated Gene 1 (NDRG1) has been mapped to human chromosome 8q24.2 with a 60 kb sequence and consists of 16 exons and 15 introns. It is present in all cells of the human body and is considered to encode a protein with a general, housekeeping function related to growth arrest, cell differentiation, organ formation, embryonic development, and maintaining the differentiating status. The expression of NDRG1 is regulated by several factors, including androgen, p53, and N-myc. Hypoxic conditions also induce NDRG1 expression via a mechanism that most likely involves nickel that interacts with the oxygen sensory pathway.(3) Pathologically, the expression of NDRG1 was previously shown to be up-regulated by the induction of differentiation in a colon carcinoma cell line.(4) More recently, NDRG1 has been associated with the progression of various human cancers, including colorectal carcinogenesis, (5) but it also seems to play an important role in the endometrial transformations leading to the completion of each menstrual cycle in humans.(6-8) It remains, however, controversial whether its overexpression suppresses or promotes tumor metastasis. (5,9,10) The phosphatase and tensin homolog deleted from chromosome10 (PTEN) gene was originally identified as a candidate tumor suppressor gene, located on chromosome 10q23.3. The PTEN gene encodes a phosphatase that dephosphorylates phosphatidylinositol-3,4,5-triphosphate.(11) It is known to play a key role in controlling cell growth, differentiation, and apoptosis.(12) Recently, the PTEN gene has been shown to be mutated or deleted in various human cancer cells.(13) The latter include prostate, breast, lung, glioblastoma, melanoma, and especially endometrial carcinoma, where deletion of PTEN was observed in more than 90% of the cases. (14,15) PTEN ...

N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin

“…The expression of NDRG1/Cap43 is often elevated in various types of malignant solid tumors, such as the lung, brain, skin, kidney, liver, and breast [11,12] and endometrial carcinoma [13], compared with their concordant normal tissues. Furthermore, expression of NDRG1/Cap43 was significantly higher in poorly differentiated carcinoma than well-differentiated carcinoma of the colon [14] and liver [15].…”

Inhibition of N-Myc down regulated gene 1 inin vitrocultured human glioblastoma cells

“…NDRG1 protein expression has been described to be present in normal brain or brain tumor tissue [11] as well as being an important gene that is playing an active role in the regulation of a broad spectrum of human cancer diseases like human gastric cancer, squamous cell carcinomas, breast cancer, human hepatocellular carcinoma, brain tumors and leukemia [12][13][14][15][16][17][18][19][20][21][22] . NDRG1 was suggested to be a prognostic marker for hypoxic regions within a tumor mass because of its stability as a protein [23][24][25] and because it is highly expressed in malignant tumor tissues compared to normal tissue of the same origin [26] .…”

Equivocal Differential Effect of NDRG1 in Human Ovarian Cancer Cells

“…Studies have shown down-regulation of NDRG1 in tumors of colon [12], breast [13] and prostate [4,9]. In contrast, NDRG1 up-regulation has been reported in hepatocellular carcinoma [14], renal cell carcinoma [15,16], and endometrial cancer [17]. NDRG1's function and regulation in cancerous human ovary is not clear.…”