This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teng, Y. Articles by Yang, X. Search for Related Content PubMed PubMed Citation Articles by Teng, Y. Articles by Yang, X.

Synergistic Function of Smad4 and PTEN in Suppressing Forestomach Squamous Cell Carcinoma in the Mouse

¹ Genetic Laboratory of Development and Diseases, Institute of Biotechnology and ² National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, P.R. China

Requests for reprints: Xiao Yang, Institute of Biotechnology, 20 Dongdajie, Fengtai, Beijing 100071, P.R. China. Phone: 86-10-63895937; Fax: 86-10-63895937; E-mail: yangx{at}nic.bmi.ac.cn.

The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have shown that coordinated deletion of the Smad4 and PTEN genes results in accelerated hair loss and skin tumor formation in mice. Herein, we exemplify that the concomitant inactivation of Smad4 and PTEN accelerates spontaneous forestomach carcinogenesis at complete penetrance during the first 2 months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathologic features of human esophageal SCCs. A small population of the SCC lesions was accompanied by adenocarcinomas at the adjacent submucosa region in the double mutant mice. The rapid progression of forestomach tumor formation in the Smad4 and PTEN double knockout mice corresponded to a dramatic increase in esophageal and forestomach epithelial proliferation. The decreased expression of p27, p21, and p16 together with the overexpression of cyclin D1 contributed cooperatively to the accelerated forestomach tumorigenesis in the double mutant mice. Our results point strongly to the crucial relevance of synergy between Smad4 and PTEN to suppress forestomach tumorigenesis through the cooperative induction of cell cycle inhibitors. (Cancer Res 2006; 66(14): 6972-81)

This article has been cited by other articles:

				Y. Gao, G. Yang, T. Weng, J. Du, X. Wang, J. Zhou, S. Wang, and X. Yang Disruption of Smad4 in Odontoblasts Causes Multiple Keratocystic Odontogenic Tumors and Tooth Malformation in Mice Mol. Cell. Biol., November 1, 2009; 29(21): 5941 - 5951. [Abstract] [Full Text] [PDF]

				F. Meng, X. Cheng, L. Yang, N. Hou, X. Yang, and A. Meng Accelerated re-epithelialization in Dpr2-deficient mice is associated with enhanced response to TGF{beta} signaling J. Cell Sci., September 1, 2008; 121(17): 2904 - 2912. [Abstract] [Full Text] [PDF]