10276

NET1

neuroepithelial cell transforming 1;NET1;neuroepithelial cell transforming 1

Rho guanine nucleotide exchange factor (GEF) 8|guanine nucleotide regulatory protein (oncogene)|neuroepithelial cell-transforming gene 1 protein|neuroepithelioma transforming gene 1|p65 Net1 proto-oncogene protein|small GTP-binding protein regulator

10p15

protein-coding

Preclinical data indicate that alpha6beta4 integrin signaling through Ras homolog gene family, member A, plays an important role in tumor cell motility. The objective of this study was to determine whether the combined expression of alpha6beta4 integrin and neuroepithelioma transforming gene 1 (Net1), a guanine nucleotide exchange factor specific for Ras homolog gene family member A, is associated with adverse clinical outcome in breast cancer patients. Immunohistochemical expression of each protein was evaluated in a tumor tissue microarray prepared from the primary tumors of 94 node-positive patients with invasive breast carcinoma treated with total mastectomy and doxorubicin-based chemotherapy without radiation with a median follow-up of 12.5 years. Associations between staining results and multiple clinicopathologic variables were investigated. Although there was no significant association between alpha6beta4 integrin or Net1 expression and clinical outcome when each marker was considered individually, coexpression of alpha6beta4 and Net1 was associated with decreased distant metastasis-free survival (P = 0.030). In the subset of patients with hormone receptor-positive tumors, coexpression of alpha6beta4 and Net1 was associated with a decrease in distant metastasis-free and overall survival (P < 0.001 and P = 0.006, respectively). Although an association between human epidermal growth factor receptor 2 expression and coexpression of alpha6beta4 and Net1 (P = 0.008) was observed, coexpression of alpha6beta4 and Net1 (hazard ratio, 1.63; P = 0.02) and lymphovascular invasion (hazard ratio, 2.35; P = 0.02) were the only factors independently associated with the development of distant metastasis in multivariate analysis. These findings suggest that coexpression of alpha6beta4 integrin and Net1 could be a useful biomarker for aggressive disease in node-positive breast cancer patients.

OBJECTIVE: Objective of this study was to detect the expression of neuroepithelial transforming gene-1 (NET-1) and proliferating cell nuclear antigen (PCNA) in hepatocellular carcinoma (HCC) and adjacent tissues, and to investigate the relation of the expression of NET-1 in HCC tissue with cancer proliferation, metastasis and clinic stages. METHODS: The expression of NET-1 mRNA was detected by reverse transcription-polymerase chain reaction method in 34 human HCC tissues, and it was matched with 34 paracarcinoma tissues. The expression of PCNA in HCC was analyzed by immunohistochemistry. Meanwhile, the relation of the expression with clinic pathological features of HCC was evaluated, and the correlation between the expression of NET-1 and PCNA in HCC was investigated. RESULTS: expression of NET-1 was significantly higher in HCC than that in matched paracarcinoma tissues. The expression of NET-1 was significantly higher in TMN III-IV HCC tissues when compared with TMN I-II HCC tissues (P<0.05). The expression level of NET-1 in HCC tissues was related to intrahepatic metastasis and portal vein infiltration. The expression of NET-1 in HCC tissues was positively correlated with PCNA. CONCLUSIONS: The expression of NET-1 may relate to proliferation, metastasis and clinic stages of HCC. The expression of NET-1 in HCC tissues may positively correlate to the TMN stages.