التفاصيل البيبلوغرافية
| العنوان: |
Synergy between von Hippel-Lindau and P53 contributes to chemosensitivity of clear cell renal cell carcinoma. |
| المؤلفون: |
ZIYI ZHAO, CHANGJIN CHEN, JUNZHI LIN, WENTONG ZENG, JUAN ZHAO, YINDAN LIANG, QINRUI TAN, CHAO YANG, HUI LI |
| المصدر: |
Molecular Medicine Reports; 2016, Vol. 14 Issue 3, p2785-2790, 6p |
| مصطلحات موضوعية: |
VON Hippel-Lindau disease, RENAL cell carcinoma, DOXORUBICIN, TUMOR proteins, CANCER chemotherapy, INHIBITION of cellular proliferation |
| مستخلص: |
The von Hippel-Lindau tumor suppressor (VHL; E3 ubiquitin ligase gene) is frequently mutated or undetectable in clear cell renal cell carcinoma (CCRCC), and therefore these tumors are highly resistant to chemotherapeutic agents, including adriamycin (ADM) and sunitinib. A mutation in the tumor protein p53 (TP53) also leads to chemoresistance in tumors; however, in CCRCC, TP53 is frequently functional, yet the tumors remain highly insensitive to chemotherapy. This indicates the possibility of a synergistic effect of VHL and P53 in CCRCC. The present study aimed to detect the chemosensitivity of CCRCC. The expression of VHL in the MZ1257 cell line sensitized these cells to ADM and sunitinib, and a knockdown of VHL in the ACHN cells increased their chemoresistance. To confirm that VHL and P53 are both required for chemosensitivity, VHL and P53 were co-expressed in 786-O cells. The results of the functional antagonist assay (which assessed the IC50 values, i.e. the half maximal inhibitory concentration) confirmed that VHL and P53 act in synergy to promote chemosensitivity. Cell cycle arrest was measured by propidium iodide staining following treatment with ADM or sunitinib. Further analysis indicated that co-expression of VHL and P53 inhibited cell proliferation by completely inhibiting the cell cycle at the G0/G1 phase, and promoted apoptosis following treatment with ADM or sunitinib. These findings demonstrated that VHL and P53 act synergistically in the regulation of cell proliferation and apoptosis in CCRCC. Overall, VHL and P53 have important roles in the regulation of cell proliferation and apoptosis in CCRCC. Furthermore, the regulatory role of VHL is dependant on the activation P53. [ABSTRACT FROM AUTHOR] |
|
Copyright of Molecular Medicine Reports is the property of Spandidos Publications UK Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder