Expression of the pro‐apoptotic protein ARTS in astrocytic tumors

• Published in: Cancer 2004-12, Vol.101 (11), p.2614-2621
• Main Authors: Gottfried, Yossi, Voldavsky, Eugene, Yodko, Lena, Sabo, Edmond, Ben‐Itzhak, Ofer, Larisch, Sarit
• Format: Article
• Language: English
• Subjects: apoptosis; ARTS; astrocytic tumors; survival rate
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20675

BACKGROUND Apoptosis (i.e., programmed cell death) plays a major role in the development of astrocytic tumors, which are the most common tumors of the central nervous system. ARTS, a proapoptotic protein that is localized in the mitochondria, promotes apoptosis by functioning as an XIAP antagonist and a caspase activator. METHODS To investigate the role of ARTS in astrocytoma, the authors examined protein expression and apoptotic activity in 72 astrocytic tumors, which included low‐grade astrocytomas, anaplastic astrocytomas, and glioblastomas. RESULTS Whereas normal astrocytes did not express the ARTS protein, astrocytoma cells strongly expressed ARTS, and the expression of this protein increased with increasing tumor grade. Furthermore, increased levels of ARTS were significantly associated with higher rates of apoptosis (as measured using the terminal deoxynucleotidyltransferase–mediated deoxyuridine triphosphate nick end‐labeling [TUNEL] assay as well as an immunohistochemical staining assay for active caspase‐3) in these tumors. Levels of two other apoptosis‐related proteins, p53 and Bcl‐2, also were examined using immunohistochemical methods; ARTS expression was found to be positively correlated with expression of the former and negatively correlated with expression of the latter, which is known to possess antiapoptotic activity. CONCLUSIONS The results of the current study suggest that ARTS levels reliably reflect the ability of cells to undergo apoptosis, which serves as a defense mechanism against the development and progression of astrocytoma. Furthermore, ARTS expression, when taken into consideration in combination with tumor grade, was the only independent predictor of survival identified in the current analysis. Thus, the authors conclude that ARTS may possess utility as a prognostic marker, as well as a therapeutic tool, for patients with astrocytoma. Cancer 2004. © 2004 American Cancer Society. ARTS, a proapoptotic mitochondrial protein that is not expressed in normal astrocytes, appears to be expressed in astrocytic tumors. ARTS expression increases with increasing astrocytoma grade and is significantly correlated with apoptotic index and patient survival. Thus, ARTS could serve as a prognostic marker, as well as a therapeutic tool, for patients with astrocytoma.