Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas

Nature 445, 656-660 (2007)

Speaker：李羽涵                            Time：2007/03/07 15:10-16:00

Commentator：徐麗君 老師                  Place：Room 601

Abstract:

p53 is a transcription protein and regulates the cell growth such as proliferation, apoptosis, and senescence. In addition, it is also a tumour suppressor protein and plays an important role for tumour cells development in many human carcinomas including liver cancer. To determine the correlation between the maintenance of tumours and the loss of p53 function, the authors used conditional RNAi to regulate p53 protein expression in a chimeric liver cancer mouse model as a strategy. Once p53 was restoration by treating tetracycline derivative, doxycycline (Dox), the tumour cells were in process of time to grow downwards, even transient expression of p53. Interestingly, ras-expressed hepatocarcinomas showed many signs of senescence following p53 reactivation, including SA-β-gal and p16, but only a few cells were undergoing apoptosis in vivo. Besides, leukocytes infiltration was detected inside of tumour tissue by microscopic examination after p53 reactivation. Furthermore, the expression of inflammatory cytokines and adhesion molecules, which involve in attracting leukocytes were up-regulated in senescence tumours. These seemed that multiple components of the innate immune system infiltrated to the site of tumours after reinstatement of p53 expression. Taken together, these results provided a novel mechanism of tumour suppression involving cooperative interactions between a tumour cell senescence program and the innate immune system. Strategies that specifically harness these processes may represent a promising therapeutic approach.

References:

1.      Staib, F. et al. 2003. TP53 and liver carcinogenesis. Hum. Mutat. 21, 201-216

2.      Xue, W. et al. 2007. Senescence and tumour clearance is triggered by p53 restoration in murine liver carcinomas. Nature 445, 656-660