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Abstract

Astrocytic tumors are the most common human brain tumors. Establishment of tumor grade is a key determinant both in the choice of a therapeutic approach and in the prognosis. The diagnosis of astrocytic tumors is currently determined following histopathological analysis. The identification of molecular markers would offer a complementary tool for characterizing tumors with respect to their clinical behavior. In this study we determined the expression levels of 3 small GTP binding proteins (RhoA, RhoB and Rac1), of their inhibitor RhoGDI and of caveolin-1 in 24 human astrocytic tumors of grades I to IV. Our results demonstrated that the expression of RhoA and RhoB decreased significantly in all brain tumors studied and was inversely related with tumor of grade II to IV malignancy. The amount of caveolin-1 immunodetected was not significantly different from normal brain samples while the Rac1 expression level was diminished in astrocytic tumors of grades III and IV. Our finding that RhoA and RhoB expression levels are correlated to tumor malignancy suggests that they may serve as novel and efficient diagnostic markers for astrocytic brain tumors of histological grade II to IV and complement currently applied histopathological analysis.

ROCK I-mediated activation of NF-κB by RhoB

“…Consistent with this, fibroblasts derived from RhoB null mice are resistant to both physical and chemical induced apoptosis [12], and RhoB induces apoptosis if overexpressed in transformed cells [9]. RhoB expression is often suppressed during tumor progression which may impair normal apoptotic signaling, and thus, support tumor growth [13][14][15]. It has been previously reported that RhoB suppresses NF-κB signaling in murine fibroblasts which may account for this propapoptotic activity [20].…”

“…Although several studies suggest that RhoB may also promote cell growth, and possess the properties of an oncogene [9,10], most studies suggest that it may in fact be a tumor suppressor [11,12]. RhoB expression is low in many tumor types [13][14][15], and knockout mice display increased susceptibility to carcinogenic agents [12]. Recent studies suggest that a change in prenylation status of RhoB may account for the proapoptotic and antineoplastic effects associated with farnesyl transferase inhibitors (FTIs) [16,17].…”

Interactions of EGFR and caveolin-1 in human glioblastoma cells: evidence that tyrosine phosphorylation regulates EGFR association with caveolae

“…Images are representative of at least four separate experiments yielding similar results different types of glioma cells; however, no comparisons with primary human astrocytes were previously made. Forget et al (2002) recently reported that immunodetected caveolin-1 protein expression in astrocytic tumors of various grades was not significantly different from that in the normal brain. In glioblastoma cells examined in this study, increases in caveolin-1 mRNA and protein expression were both correlated with the more transformed cellular phenotype, and consistently detected in glioblastoma tumors, suggesting a role for caveolin-1 in glial tumorigenesis.…”

RhoB Protects Human Keratinocytes from UVB-induced Apoptosis through Epidermal Growth Factor Receptor Signaling

“…Although some GTPase family members, such as RhoA, Rac1, and Cdc42, promote oncogenesis, invasion, and metastasis, there is emerging evidence that points to a tumor-suppres-sive role for RhoB (9 -12), notably through its role in the apoptotic process (9,13,14). Besides the fact that ectopic expression of RhoB inhibits tumor growth (9,15) and melanoma metastasis in a mouse model (16), we (17) and others (18,19) have also shown that RhoB expression decreases substantially with the aggressiveness of lung, head, and neck carcinomas and glioblastomas.…”