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This Article Full Text Full Text (PDF) All Versions of this Article: 10/6/958    most recent 15228517-2008-054v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mucignat-Caretta, C. Articles by Caretta, A. Search for Related Content PubMed PubMed Citation

Selective distribution of protein kinase A regulatory subunit RII in rodent gliomas

Department of Human Anatomy and Physiology, University of Padova, Padova (C.M.-C., A.Cav., M.R., A.Car.) and Department of Biomedical and Morphological Sciences, Section of Anatomy and Histology, University of Verona, Verona (M.M., C.Z.); Italy

Address correspondence to Carla Mucignat-Caretta, Department of Human Anatomy and Physiology, University of Padova, Via Marzolo 3, 35131 Padova, Italy (carla.mucignat{at}unipd.it).

Differential diagnosis of brain tumor types is mainly based on cell morphology and could benefit from additional markers. The cAMP second-messenger system is involved in regulating cell proliferation and differentiation and is conceivably modulated during cancer transformation. The cAMP second-messenger system mainly activates protein kinases, which are in part docked to cytoskeleton, membranes, or organelles by anchoring proteins, forming protein aggregates that are detergent insoluble and not freely diffusible and that are characteristic for each cell type. The intracellular distribution of the detergent-insoluble regulatory subunits (R) of the cAMP-dependent protein kinase has been examined in mouse and rat glioma cells both in vitro and in vivo by immunohistochemistry. In normal rodent brains, the RII regulatory subunit is detergent insoluble only in ependymal cells, while in the rest of the brain it is present in soluble form. Immunohistochemistry shows that in both mouse and rat glioma cell lines, RII is mainly detergent insoluble. RII is localized close to the nucleus, associated with smooth vesicles in the trans-Golgi network area. Both paclitaxel and vinblastine cause a redistribution of RII within the cell. Under conditions that increased intracellular cAMP, apoptosis of glioma cells was observed, and it was accompanied by RII redistribution. Also in vivo, detergent-insoluble RII can be observed in mouse and rat gliomas, where it delineates the border between normal brain tissue and glioma. Therefore, intracellular distribution of detergent-insoluble RII can assist in detecting tumor cells within the brain, thus making the histologic diagnosis of brain tumors more accurate, and may represent an additional target for therapy.

Key Words: cAMP • diagnosis • glioblastoma • Golgi • protein kinase A