Tam Chun Wai, Liu Vincent Wing Sun, Leung Wai Ying, Yao Kwok-Ming, Shiu Stephen Yuen Wing
Department of Physiology, The University of Hong Kong, Laboratory Block, Faculty of Medicine Building, Hong Kong, China.
Cancer Lett. 2008 Nov 18;271(1):64-80. doi: 10.1016/j.canlet.2008.05.047. Epub 2008 Jul 17.
Tumor suppressive actions of the autocrine human secreted PDZ domain-containing protein 2 (sPDZD2) have been reported, but the mechanisms remain enigmatic. Here, we showed that sPDZD2 induced senescence of prostate cancer DU145 cells, quiescence of breast cancer MCF-7 and liver cancer Hep-G2 cells, via transcriptional activation of mutant or wild-type p53. Furthermore, sPDZD2 sensitized mutant p53-positive DU145 cells and wild-type p53-positive MCF-7 cells to apoptosis induction through genotoxic stress imposed by sub-lethal concentration of hydrogen peroxide. Together, our findings suggest a potential autocrine pathway of p53 activation by transcriptional regulation, and a new approach to reactivate p53 for cancer therapy.
已有报道称自分泌的人源含PDZ结构域蛋白2（sPDZD2）具有肿瘤抑制作用，但其机制仍不清楚。在此，我们发现sPDZD2通过突变型或野生型p53的转录激活诱导前列腺癌DU145细胞衰老、乳腺癌MCF-7细胞和肝癌Hep-G2细胞静止。此外，sPDZD2通过亚致死浓度过氧化氢施加的基因毒性应激使突变型p53阳性的DU145细胞和野生型p53阳性的MCF-7细胞对凋亡诱导敏感。总之，我们的研究结果提示了一种通过转录调控激活p53的潜在自分泌途径，以及一种重新激活p53用于癌症治疗的新方法。
