Purpose: The present study was aimed at clarifying the expression of astrocyte elevated gene-1 (AEG-1), one of the target genes of oncogenic Ha-ras, in breast cancer and its correlation with clinicopathologic features, including the survival of patients with breast cancer. Experimental Design: The expression of AEG-1 in normal breast epithelial cells, breast cancer cell lines, and in four cases of paired primary breast tumor and normal breast tissue was examined using reverse transcription-PCR and Western blot. Real-time reverse transcription-PCR was applied to determine the mRNA level of AEG-1 in the four paired tissues, each from the same subject. Furthermore, AEG-1 protein expression was analyzed in 225 clinicopathologically characterized breast cancer cases using immunohistochemistry. Statistical analyses were applied to test for the prognostic and diagnostic associations. Results: Western blot and reverse transcription-PCR showed that the expression level of AEG-1 was markedly higher in breast cancer cell lines than that in the normal breast epithelial cells at both mRNA and protein levels. AEG-1 expression levels were significantly up-regulated by up to 35-fold in primary breast tumors in comparison to the paired normal breast tissue from the same patient. Immunohistochemical analysis revealed high expression of AEG-1in 100 of 225 (44.4%) paraffin-embedded archival breast cancer biopsies. Statistical analysis showed a significant correlation of AEG-1 expression with the clinical staging of the patients with breast cancer (P = 0.001), as well as with the tumor classification (P = 0.004), node classification (P = 0.026), and metastasis classification (P = 0.001). Patients with higher AEG-1 expression had shorter overall survival time, whereas patients with lower AEG-1 expression had better survival. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of patients with breast cancer. Conclusions: Our results suggest that AEG-1 protein is a valuable marker of breast cancer progression. High AEG-1expression is associated with poor overall survival in patients with breast cancer.

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Purpose: To characterize the expression of sphingosine kinase-1 (SPHK1) in human astrocytomas and to investigate the association between SPHK1 expression and progression of astrocytomas. Experimental Design: The expression of SPHK1in normal human astrocytes, astrocytoma cell lines, and four pairs of matched astrocytoma tissues and their adjacent normal brain tissues were detected by quantitative reverse transcription-PCR and Western blot. In addition, SPHK1protein expression was examined in 243 cases of histologically characterized astrocytomas by immunohistochemistry. Statistical analyses were applied to test for prognostic and diagnostic associations. Results: SPHK1in astrocytoma cell lines was elevated at both mRNA and protein levels, and the SPHK1mRNA and protein were significantly up-regulatedby up to 6.8-and 40-fold, respectively, in primary astrocytomas compared with those in the adjacent noncancerous brain tissues. Immunohistochemical analysis showed that 100 of 243 (41.2%) paraffin-embedded archival astrocytoma biopsies exhibited high expression of SPHK1. Statistical analysis suggested that the up-regulation of SPHK1was significantly correlated with the histologic grade of astrocytoma (P = 0.000) and that patients with high SPHK1level exhibited shorter survival time (P < 0.001). Multivariate analysis revealed that SPHK1up-regulation might be an independent prognostic indicator for the survival of patients with astrocytoma. Conclusions: SPHK1might represent a novel and useful prognostic marker for astrocytoma and play a role during the development and progression of the disease.

One of the features of malignant gliomas is their deviant resistance to cellular apoptosis induced by cytotoxic reagents. Bmi-1, an oncoprotein, has been linked to oncogenesis and cancer progression in various types of human cancers including gliomas. However, the mechanisms underlying Bmi-1 antiapoptotic function remain largely unknown. In this study, we report that Bmi-1 renders apoptotic resistance to glioma cells through nuclear factor-B (