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Grade‐dependent expression and subcellular distribution of JAZ in human gliomas
Author(s) -
Qiu Jingxin,
Yang Mingli,
May W. Stratford,
Liu Chen,
Friedman William A.,
Yachnis Anthony
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a393
Subject(s) - cytoplasm , immunostaining , microbiology and biotechnology , biology , glioma , rna , immunohistochemistry , cancer research , gene , genetics , immunology
JAZ is a novel dsRNA binding zinc finger protein that can mediate G1 cell cycle arrest and apoptosis by positively regulating p53 transcriptional activity. JAZ has also been reported as a cargo protein of exportin‐5, suggesting a possible role in micro‐RNA processing. Since JAZ is abundantly expressed in mouse brain tissue, we further explored JAZ expression in human brain tissue. A tissue microarray (TMA) was constructed that contains 90 tissue cores representing a spectrum of infiltrating gliomas and non‐neoplastic normal brain. The TMA was probed for JAZ expression by immunohistochemistry and immunofluorescence. We found that JAZ is normally expressed in the cytoplasm of CNS neurons. However, while not expressed in normal glial cells, JAZ is abundantly expressed in malignant gliomas with an unusual, predominantly cytoplasmic immunostaining pattern. Levels of immunoreactivity are tumor grade‐dependent with the highest expression in glioblastoma multiforme. Interestingly, JAZ appeared to be redistributed from the cytoplasm into the nucleus around the areas of pseudopalisading necrosis, in which tumor cells are believed to be hypoxic. Such cytoplasmic to nuclear redistribution is also observed in human CNS neurons under conditions of hypoxia‐ischemia. Our findings suggest a role for JAZ in glioma progression by mechanisms potentially involving interaction with p53 and/or possibly micro‐RNA transport.