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Coordinated p27 Kip1 expression as a function of distance between crypts ‐ Potential inter‐crypt signaling
Author(s) -
Hong Mee Young,
Baladandayuthapani Veerabhadran,
Li Yehua,
Carroll Raymond J,
Turner Nancy D.,
Lupton Joanne R
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.865.4
Subject(s) - crypt , biology , aberrant crypt foci , carcinogenesis , correlation , cell cycle , microbiology and biotechnology , apoptosis , colorectal cancer , genetics , endocrinology , cancer , mathematics , colonic disease , geometry
Colonic epithelial cells are arranged in patterns called crypts. There has been a conjecture that a coordinated response exists at the crypt level, i.e. that biological responses in one crypt affects the biological responses in neighboring crypts. P27Kip1 (p27) is a cyclin dependent kinase inhibitor, which arrests cell cycle progression and induces apoptosis. We hypothesized if a crypt has high p27 expression, the neighboring crypts are likely to have high p27 expression. To test the hypothesis, 20 colonic crypts in each of 12 rats were analyzed for p27 levels and the distance between the crypts were measured. The correlation between the p27 expression between the crypts were analyzed using Bayesian statistical methods. The correlation at 25 μm was 0.57 and the correlation was positive for distances up to 400 μm (p<0.05). The closer crypts were to one another the better the correlation. This observation supports the existence of inter‐crypt signaling; p27 expression in crypts which are in close proximity tend to have similar expression levels. This type of inter‐crypt signaling may be responsible for the formation of aberrant crypt foci, polyps and eventually colon adenomas. This spatial analysis is a novel mathematical approach to study of colon carcinogenesis. Funded by NIH (CA61750, CA82907, CA59034), NSBRI NASA NCC 9–58 and NIEHS P30‐ES09106.