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Shift in $AP-2\alpha$ Localization Characterizes Astrocytoma Progression

Britto, Ramona and Umesh, S and Hegde, AS and Hegde, Sridevi and Santosh, Vani and Chandramouli, BA and Somasundaram, Kumaravel (2007) Shift in $AP-2\alpha$ Localization Characterizes Astrocytoma Progression. In: Cancer Biology & Therapy, 6 (3). pp. 413-418.

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Activator protein $2\alpha$ $(AP‑2\alpha)$ has been shown to be lost in the advanced stages of many cancers, including gliomas. In this study, we wanted to analyze the expression of $(AP‑2\alpha)$ in astrocytoma samples of different grades both at the RNA level, by real‑time qPCR and at the protein level, by immunohistochemistry, and to examine its correlation, if any, with patient outcome. Five Grade I, 14 Grade II, 18 Grade III, 72 Grade IV samples and 13 normal brain controls were included. We did not find any clear pattern of regulation at the RNA level with tumor grade. The RNA expression levels however, correlated to a large extent with the nuclear $(AP‑2\alpha)$ staining in these samples (72.09%; 31/43). Further, we did not find a complete loss of nuclear $(AP‑2\alpha)$ expression in the higher grades, in contrast to previous reports. Interestingly, we found cytoplasmic $(AP‑2\alpha)$ expression in a majority of higher grade astrocytomas (Grade IV—85%; 33/39 and Grade III—74%; 14/19) in comparison to lower grades (Grade I—0%; 0/5 and Grade II—37.5%; 3/8) suggesting that the translocation of this protein from the nucleus to the cytoplasm may be responsible for the increased malignancy. The nuclear expression in these grades was found to be concomitantly reduced. Within GBMs, we found that decreased nuclear expression was indicative of a better prognosis. The striking observation was the shift in localization of this protein from the nucleus to the cytoplasm with increasing tumor grade, pointing to a crucial role for this transcription factor in the progression of astrocytomas.

Item Type: Journal Article
Publication: Cancer Biology & Therapy
Publisher: Landes Bioscience
Additional Information: Copyright of this article belongs to Landes Bioscience.
Keywords: AP-2;cancer;glioma;astrocytoma;glioblastoma multiforme.
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 12 Jun 2008
Last Modified: 19 Sep 2010 04:45
URI: http://eprints.iisc.ac.in/id/eprint/14271

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