Synergistic function of Smad4 and PTEN in suppressing forestomach squamous cell carcinoma in the mouse
The genetic bases underlying esophageal tumorigenesis are poorly understood. Our previous studies have demonstrated 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 two months of age. All of the forestomach tumors were invasive squamous cell carcinomas (SCCs), which recapitulated the natural history and pathological features of human esophageal squamouus cell carcinomas (ESCCs). 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 forestormach tumorigenesis through the cooperative induction of cell cycle inhibitors.
滕艳 Yan Teng 孙安娜 An-Na Sun 潘晓晨 Xiao-Chen Pan 杨冠 Guan Yang 杨蕾蕾 Lei-Lei Yang 王明荣 Ming-Rong Wang 杨晓 Xiao Yang
军事医学科学院生物工程研究所,发育和疾病遗传学研究室,北京,100071 Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, 100071 中国医学科学院肿瘤研究所,北京,100071 National Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Pe
国际会议
武夷山
英文
64-73
2006-08-19（万方平台首次上网日期，不代表论文的发表时间）