Frequent and variable abnormalities in p14 tumor suppressor gene in glioma cell lines |
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Authors: | Yoshiyuki Tanaka Shu-Jing Zhang Hiroshi Terasaki Hisashi Koga Sumio Endo Hiroshi Usui Kazuo Washiyama Toshiro Kumanishi Yuji Uematsu Toru Itakura |
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Institution: | (1) Neurological Surgery, Wakayama Medical University, Wakayama, Japan;(2) Molecular Neuropathology, Brain Research Institute, Niigata University, Niigata, Japan;(3) Department of Bioscience and Nutrition, Karolinska Institute, Huddinge, Sweden;(4) Mitsubishi Kagaku Bio-Clinical Laboratories, Tokyo, Japan;(5) Laboratory of Medical Genomics, Department of Human Genome Technology, Kazusa DNA Research Institute, Chiba, Japan;(6) Niigata Longevity Research Institute, 766 Shimoishikawa, Shibata, Niigata 959-2516, Japan |
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Abstract: | Ten glioma cell lines were examined for abnormalities of exon 1β of the p14 gene and then for abnormalities of the entire
p14 gene with the use of previous findings of other exons. Abnormalities of exon 1β and the entire p14 gene were detected
in eight of ten cases: homozygous deletion of the entire gene in six cases, hemizygous deletion of exon 1β with homozygous
deletion of downstream exons in one case, and hemizygous deletion of the entire coding region with a missense mutation (A97V)
at the C-terminal nucleolar localization domain in one case. The remaining two cases revealed tno such abnormalities. p14
gene expression was observed in the latter two cases and one case with A97V mutation in the hemizygously deleted coding region,
but not in the others, including one case with only exon 1β. In the three cases with p14 gene expression, immunocytochemistry
revealed p14 nucleolar staining, suggesting the retention of the functional activity of p14 protein and, in the case with
the A97V mutation, an insufficient mutational effect as well. The present findings of the frequent and variable p14 gene abnormalities,
including rare-type ones with or without sufficient mutational effect in glioma cell lines, might be of value for better understanding
of the p14 gene and its related pathways in glioma carcinogenesis. |
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Keywords: | p14 gene Glioma cell line MDM2 gene p14-MDM2-p53 pathway |
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