Department of Medicine, Division of Digestive and Liver Diseases, Columbia University Medical Center, New York 10032, USA.
Cancer Invest. 2012 May;30(4):275-86. doi: 10.3109/07357907.2012.657814. Epub 2012 Apr 5.
Transgenic mice overexpressing human progastrin (hGAS) show colonic crypt hyper-proliferation and elevated susceptibility to colon carcinogenesis. We aimed to investigate effects of p53 mutation on colon carcinogenesis in hGAS mice. We show that introducing a p53 gene mutation further increases progastrin dependent BrdU labeling and results in markedly elevated number of aberrant crypt foci (ACF) and colonic tumors. We demonstrate that hGAS/Lgr5-GFP mice have higher number of Lgr5+ colonic stem cells per crypt when compared to Lgr5-GFP mice indicating that progastrin changes crypt biology through increased stem cell numbers and additional p53 mutation leads to more aggressive phenotype in this murine colon cancer model.
过表达人胃泌素原（hGAS）的转基因小鼠表现出结肠隐窝过度增殖，并易发生结肠癌。我们旨在研究 p53 突变对 hGAS 小鼠结肠癌发生的影响。我们发现，引入 p53 基因突变进一步增加了胃泌素依赖性 BrdU 标记，并导致异常隐窝灶（ACF）和结肠肿瘤数量明显增加。我们证明，与 Lgr5-GFP 小鼠相比，hGAS/Lgr5-GFP 小鼠每个隐窝的 Lgr5+结肠干细胞数量更高，这表明胃泌素通过增加干细胞数量改变隐窝生物学，而额外的 p53 突变导致这种小鼠结肠癌模型更具侵袭性表型。
