Homeobox Msx1 Interacts with p53 Tumor Suppressor and Inhibits Tumor Growth by Inducing Apoptosis

Speaker: 鄭智仁                    Time: PM 3:00-4:00; 6/8/2005

Commentator: 周楠華 醫師           Place: 601

Abstract:

Several cellular responses are modulated by p53, including cell-cycle arrest, senescence, differentiation and apoptosis. In some human cancers, interaction of p53 with viral or cellular proteins leads to inactivation of p53 functions. Thus, restoration of wild-type p53 activity in tumor cells is of considerable therapeutic potential. The functions of p53 could be regulated by several mechanisms, including post-translational modification, stabilization, protein interactions, and subcellular localization. The authors have reported that expression of Msx1 was lower in cervical cancer tissue than normal controls. The Msx1 protein is a homeoprotein and functions as a transcriptional repressor. It is expressed at sites where cellular proliferation and apoptosis occur during embryogenesis. In this study, Msx1 was demonstrated to stabilize the p53. By using yeast two-hybrid assay, homeodomain of Msx1 was discovered to interact with p53. Co-transfection of p53-null human lung carcinoma H1299 cells with wild-type p53 and full-length Msx1 revealed that level of p53 protein showed a positive association with amounts of Msx1 protein. In nude mice experiment, overexpression of Msx1 suppressed the tumor growth, consistent with experimental data in vitro. Taken together, identification of interacting proteins of Msx1 or its target genes may have potential in developing therapeutic regimen for cancer prevention or targeting therapy for tumors with impaired p53 function.

References:

1.     Vousden KH, Lu X. Live or let die: the cell’s response to p53. Nat Rev Cancer 2002;2:594–604.

2.     Park J, Park K, Kim S, Lee JH. Msx1 gene overexpression induces G1 phase cell arrest in human ovarian cancer cell line OVCAR3. Biochem Biophys Res Commun2001;281:1234–40.

3.     Park K, Kim K, Rho SB, Choi K, Kim D, Oh SH, Park J, Lee SH, Lee JH. Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis. Cancer Res. 2005 Feb 1;65(3):749-57.