53BP1 functions as a tumor suppressor in breast cancer via the inhibition of NF-κB through miR-146a
Menée in vitro et in vivo, cette étude met en évidence un mécanisme par lequel, en régulant de façon négative l'expression du facteur NF-κB, la protéine 53BP1 exerce un rôle de suppresseur de tumeurs dans le cancer du sein
p53-binding protein-1 (53BP1) plays a critical role in cell cycle checkpoint and DNA repair activities. Recently, 53BP1 was recognized as a potential tumor suppressor gene. In this report, we investigated its tumor suppressor function in breast cancer. In clinical samples, we observed a lower level of 53BP1 expression in the cancer lesions than in the matched non-tumor tissues. Furthermore, the 53BP1 level showed a gradual decrease during the progression from precancerous to cancer lesion. Ectopic expression of 53BP1 can significantly inhibit cell proliferation and curb the invasiveness in breast cancer cell lines, while knockdown of 53BP1 by RNA interference had the opposite effects.. Additionally, 53BP1 markedly inhibited xenograft formation and metastasis of breast cancer cells in nude mice. Both in vitro and vivo studies revealed that the 53BP1 expression level was inversely correlated to the function of nuclear factor kB (NF-κB), which contributes to the invasion and metastasis of breast cancer. Importantly, the inhibitory effect of 53BP1 on NF-κB activity was shown to be mediated by the upregulation of miR-146a. Together, our findings demonstrated that 53BP1 has a potent tumor suppressor activity in breast cancer and it may serve as a novel target for breast cancer prevention and treatment.
http://carcin.oxfordjournals.org/content/early/2012/09/22/carcin.bgs298.abstract