May astrocyte-elevated gene-1 is a novel predictor of poor prognosis for cancer patients?

Abstract

Astrocyte-elevated gene-1 was cloned as a human immunodeficiency virus-1-inducible and tumor necrosis factor-α-inducible transcript in primary human fetal astrocytes by a rapid subtraction hybridization approach. Astrocyte-elevated gene-1 down-regulates the expression of the glutamate transporter excitatory amino acid transporter 2, thus, it is implicated in glutamate-induced excitotoxic damage to neurons as evident in human immunodeficiency virus-associated neurodegeneration. However, accumulating evidences imply that astrocyte-elevated gene-1 might play a pivotal role in the pathogenesis, progression and metastasis of diverse cancers. Astrocyte-elevated gene-1 expression is elevated in diverse cancers, overexpression of astrocyte-elevated gene-1 increases while siRNA inhibition of astrocyte-elevated gene-1 decreases migration and invasion of cancer cells, respectively. Astrocyte-elevated gene-1 exerts its effects by activating the nuclear factor kappa B pathway, the oncogenic Ha-ras could up-regulate astrocyte-elevated gene-1 expression by inducing the binding of c-Myc to the astrocyte-elevated gene-1 promoter and astrocyte-elevated gene-1 inhibited prostate cancer progression through up-regulation of FOXO3a activity. These provocative findings are intensifying interest in astrocyte-elevated gene-1 as a crucial regulator of tumor progression and metastasis and as a potential mediator of neurodegeneration. The evidences to show the expression of astrocyte-elevated gene-1 in breast cancer and its correlation with clinicopathologic features, including the survival of patients with breast cancer confirm the hypotheses that astrocyte-elevated gene-1 is a novel predictor of poor prognosis for cancer patients.