TY - JOUR AB - In gliomas, a high frequency of homozygous p16 gene deletions have been demonstrated, which are believed to be linked with malignant progression. The aim of this study was to assess the role of p16 in growth, invasion, and senescence. The human glioma cell lines U87 MG and U373 MG were transduced with Ad-p16, and cell viability was assessed by trypan blue staining. To examine the mechanism of cell growth inhibition, cell cycle analyses and annexin assays were performed. The invasive potential of Ad-p16 transduced cells was evaluated using a Matrigel invasion assay, and trimolecular complex (MMP-2/MT1-MMP/TIMP-2) synthesis was proven by zymography and Western blotting. To establish the link between p16 and cell senescence, we stained for Senescence-Associated β-galactosidase activity. A cell proliferation assay demonstrated that Ad-p16 treatment significantly inhibits cell growth. Moreover, this cell growth inhibition was induced by cell cycle arrest, not by apoptosis. In vitro treatment of malignant glioma cells with Ad-p16 significantly decreased their invasive potential by Matrigel invasion assay. However, we were unable to demonstrate any differences in the constitutive productions and secretions of MMP-2, MT1-MMP, and TIMP-2, among the mock-treated, Ad-lacZ-transduced, and Ad-p16-transduced cells. p16 expression caused an enlargement of all cells, and these were morphologically similar to senescent cells. Staining for Senescence-Associated β-galactosidase activity showed that the enlarged cells stained positively. Taken together these data strongly suggest that the anti-cancer effect of p16 is modulated by p16-mediated cell cycle arrest and by the induction of senescence. AD - Department of Neurosurgery, Seoul National University, College of Medicine, Seoul, Korea null AU - Kim,Seung-Ki AU - Wang,Kyu-Chang AU - Cho,Byung-Kyu AU - Lim,Su-Young AU - Kim,Young-Yim AU - Oh,Chang-Wan AU - Chung,You-Nam AU - Kim,Chae-Yong AU - Lee,Choon-Taek AU - Kim,Hyun,Jib DA - 2003/09/01 DO - 10.3892/or.10.5.1121 EP - 1126 IS - 5 JO - Oncol Rep PY - 2003 SN - 1021-335X 1791-2431 SP - 1121 ST - Adenoviral p16/CDKN2 gene transfer to malignant glioma: Role of p16 in growth, invasion, and senescence T2 - Oncology Reports TI - Adenoviral p16/CDKN2 gene transfer to malignant glioma: Role of p16 in growth, invasion, and senescence UR - https://doi.org/10.3892/or.10.5.1121 VL - 10 ER -