期刊
GASTROENTEROLOGY
卷 123, 期 3, 页码 751-763出版社
W B SAUNDERS CO
DOI: 10.1053/gast.2002.35382
关键词
-
资金
- NCI NIH HHS [CA-63507, CA88460] Funding Source: Medline
Background & Aims: APC gene mutation is an early alteration in most colorectal tumors. In an attempt to determine its role in tumor development, we asked whether reintroducing wild-type APC into colorectal cancer cells with mutant APC affected cell cycle progression. Methods: Using transient transfection, a plasmid containing the APC complementary DNA and DNA encoding the green fluorescent protein was expressed in SW480 cells. In addition, several other constructs were co-expressed with APC to determine their combined effects. Results: We report that colorectal cancer cell lines transfected with wild-type APC arrest in the G(1)-phase of the cell cycle and that this arrest is abrogated by cotransfecting constitutively active beta-catenin or cyclin D1 and cMYC together. This APC-induced cell cycle arrest involves the disruption of beta-catenin-mediated transcription and depends on components of the G(1)/S regulatory machinery, as overexpression of E1a or E2F-1, -2, or -3 overrides the G(1) arrest. Consistent with this, APC transfection inhibits RB phosphorylation and reduces levels of cyclin D1. Conclusions: Our results suggest that APC functions upstream of RB in the G(1)/S regulatory pathway, cyclin D1 and cMYC affect APC-mediated arrest equivalently to oncogenic beta-catenin, and most colon tumors disrupt control of G(1)/S progression by APC mutation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据