Abstract:
: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.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Philipp-Staheli J,Kim KH,Payne SR,Gurley KE,Liggitt D,Longton G,Kemp CJdoi
10.1016/s1535-6108(02)00054-5keywords:
subject
Has Abstractpub_date
2002-05-01 00:00:00pages
355-68issue
4eissn
1535-6108issn
1878-3686pii
S1535610802000545journal_volume
1pub_type
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