共 77 条
Pathway-specific tumor suppression:: Reduction of p27 accelerates gastrointestinal tumorigenesis in Apc mutant mice, but not in Smad3 mutant mice
被引:72
作者:

Philipp-Staheli, J
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机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Kim, KH
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h-index: 0
机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Payne, SR
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h-index: 0
机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Gurley, KE
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h-index: 0
机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Liggitt, D
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h-index: 0
机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Longton, G
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h-index: 0
机构: Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA

Kemp, CJ
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h-index: 0
机构:
Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA
机构:
[1] Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA
[3] Univ Washington, Sch Med, Dept Comparat Med, Seattle, WA 98195 USA
来源:
基金:
美国国家卫生研究院;
关键词:
D O I:
10.1016/S1535-6108(02)00054-5
中图分类号:
R73 [肿瘤学];
学科分类号:
100214 ;
摘要:
Expression of the cyclin-dependent kinase inhibitor p27(Kip1) (p27) is frequently reduced in human colorectal cancer, and this correlates with poor patient prognosis. To clarify the role of p27 in gastrointestinal (GI) cancer, we measured p27 expression, as well as the effect of germline deletion of p27, in 3 different mouse models of GI neoplasia. p27 expression was frequently reduced in GI tumors arising in 1,2-dimethylhydrazine (DMH) treated mice, and in Apc mutant Min/+ mice, but not in GI tumors arising in Smad3 mutant mice. Germline deletion of p27 resulted in accelerated tumor development and increased tumor cell proliferation in both DMH treated and Min/+ mice, but not in Smad3 mutant mice. p27 deficiency also led to increased adenoma to adenocarcinoma progression. These results indicate that reduction of p27 cooperates with mutations in Apc but not in Smad3 during GI tumorigenesis. Thus, tumor suppression by p27 is contingent on the specific oncogenic pathway that drives tumor development.
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页码:355 / 368
页数:14
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