[Expression and significance of new candidate tumor suppressor gene N-Myc downstream-regulated gene 2 in colorectal cancer].

OBJECTIVE: To determine the expression of new candidate tumor suppressor gene N-Myc downstream-regulated gene 2(Ndrg2) in colorectal cancer with different differentiation, and analyze its clinical significance. METHODS: Specimens of 50 colorectal cancer patients with different differentiation were collected. Immunohistochemistry and Western blot were used to examine the expression of Ndrg2. Colorectal cancer tissue array in large scale was applied to analyze the expression of Ndrg2 and the statistics analysis was performed referring to the patients information of the array. RESULTS: Among 50 cases, Ndrg2 expression level of colorectal cancer was significantly lower in 32 cases as compared to adjacent and normal tissue of the same individual, while Ndrg2 expression of adjacent tissue was significantly lower than that of normal tissue. Ndrg2 protein levels increased from poor-differentiated to well-differentiated carcinomas(P=0.005). CONCLUSIONS: The expression of Ndrg2 in different differentiated colorectal cancer tissues show a significant distinction. Ndrg2 may be involved in the regulation of differentiation in colorectal cancer.

Role of PI3K/Akt and MEK/ERK in mediating hypoxia-induced expression of HIF-1alpha and VEGF in laser-induced rat choroidal neovascularization.

PURPOSE: The transcription factor hypoxia-inducible factor (HIF)-1 plays a central physiological role in oxygen and energy homeostasis and is activated during hypoxia by stabilization of the subunit HIF-1alpha. Hypoxia plays an important role in the development of choroidal neovascularization (CNV). Expression of HIF-1alpha has been demonstrated in CNV. Vascular endothelial growth factor (VEGF) is one of the most well-characterized angiogenic factors in CNV, which is under the regulation of HIF-1. The aim of the present study was to explore the upstream signaling pathways involved in regulating hypoxia-induced expression of HIF-1alpha and VEGF in laser-induced rat CNV. METHODS: A well-established rat model of CNV and cultured human retinal pigment epithelium (hRPE) was used to investigate the role of PI3K/Akt and MEK/ERK pathways in regulating HIF-1alpha and VEGF expression in CNV in rat and hRPE under hypoxia by immunohistochemistry, Western blot analysis, real-time PCR, and ELISA. RESULTS: pAkt, pERK, HIF-1alpha, and VEGF were upregulated in vivo and in vitro. PI3K inhibitor (Ly294002) significantly decreased pAkt activity and HIF-1alpha and VEGF expression in vivo and in vitro, whereas MEK inhibitor (PD98059) reduced ERK phosphorylation and the expression of VEGF but had no effect on HIF-1alpha. LY294002 and PD98059 severely inhibited the formation of CNV. CONCLUSIONS: The PI3K/Akt pathway was required for hypoxia-induced expression of HIF-1alpha and VEGF, whereas the MEK/ERK pathway was required only for VEGF in laser-induced rat CNV.

[Expression of candidate tumor suppressor gene N-Myc downstream-regulated gene 2 in colon cancer].

OBJECTIVE: To analyze the expression level of candidate tumor suppressor gene N-Myc downstream-regulated gene 2 (NDRG2) in human colon cancer. METHODS: Thirty samples of colon cancer tissues with matched normal colon tissues were collected. The NDRG2 mRNA level was detected by semi-quantitive RT-PCR and the NDRG2 protein level was examined by Western blot and immunohistochemistry. RESULTS: Twelve samples of colon cancer tissues had low NDRG2 mRNA level and low protein level. The positive rates of NDRG2 in normal tissues and the tumorous colon tissues were 90.0%(27/30) and 53.3%(16/30) by immunohistochemistry respectively. There was a significant difference between two groups (P<0.05). The NDRG2 expression was not correlated with age, sex, metastasis of lymph node, depth of infiltration, as well as the Dukes staging(P>0.05), while it was correlated to the histology grading. The positive rate of NDRG2 in the well- and moderate-differentiation group was higher than that in the poor-differentiation group(P<0.05). CONCLUSION: The expression of NDRG2 is low in some colon cancer tissues, which indicates that the low level of NDRG2 expression may be engaged in the development of colon cancer.