Sign up for Table of Contents Alerts.
Email this page
Print this page
Research Paper
p14ARF Sensitizes Human Osteosarcoma Cells to Cisplatin-Induced Apoptosis in a p53-Independent Manner
Xiang-Wei Yuan, Xiao-Feng Zhu, Xiu-Fang Huang, Pu-Yi Sheng, Ai-Shan He, Zi-Bo Yang, Rong Deng, Gong-Kan Feng and Wei-Ming Liao
volume 6 | issue 7
July 2007Pages: 1074 - 1080
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.
The tumor suppressor p14ARF, encoded by the INK4a/ARF locus, is often disrupted in human cancers. p14ARF triggers cell cycle arrest and sensitizes cells to apoptosis in the presence of collateral signals. To investigate the role of p14ARF in chemotherapeutic drugs-induced apoptosis, p14ARF was overexpressed by stable transfection in human osteosarcoma cell lines, U2OS (p53-wt/p14ARF-null) and MG63 (p53-mt/p14ARF-null). The results showed that ectopic p14ARF sensitized both cell lines to cisplatin-induced cytotoxicity and apoptosis. This sensitization of cisplatin-induced apoptosis was associated with upregulation of p53, Bax and p21 in U2OS cells. Conversely, such a result was not observed in MG63 cells. Moreover, the sensitization of cisplatin-induced cytotoxicity in U2OS cells was unaltered by p53 siRNA. Together, we show here p14ARF sensitizes human osteosarcoma cells to cisplatin-induced apoptosis by in a p53-independent manner. Proper combinations of p14ARF gene transfer and conventional chemotherapy may be a valuable strategy in human osteosarcoma treatment.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDFIf the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.