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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2000-8-23
pubmed:abstractText
We have recently demonstrated that overexpression of PKC beta(II) renders transgenic mice more susceptible to carcinogen-induced colonic hyperproliferation and aberrant crypt foci formation. In order to further investigate the ability of PKC beta(II) to modulate colonocyte cytokinetics, we determined the localization of PKC beta(II) with respect to cell proliferation and apoptosis along the entire colonic crypt axis following carcinogen and diet manipulation. Rats were provided diets containing either corn oil [containing n-6 polyunsaturated fatty acids (PUFA)] or fish oil (containing n-3 PUFA), cellulose (non-fermentable fiber) or pectin (fermentable fiber) and injected with azoxymethane (AOM) or saline. After 16 weeks, an intermediate time point when no macroscopic tumors are detected, colonic sections were utilized for immunohistochemical image analysis and immunoblotting. Cell proliferation was measured by incorporation of bromodeoxyuridine into DNA and apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling. In the distal colon, PKC beta(II) staining was localized to the upper portion of the crypt. In comparison, proximal crypts had more (P < 0.05) staining in the lower tertile. AOM enhanced (P < 0.05) PKC beta(II) expression in all regions of the distal colonic crypt (upper, middle and lower tertiles). There was also an interaction (P < 0.05) between dietary fat and fiber on PKC beta(II) expression (corn/pectin > fish/cellulose, fish/pectin > corn/cellulose) in all regions of the distal colonic crypt. With respect to colonic cell kinetics, proliferation paralleled the increase in PKC beta(II) expression in carcinogen-treated animals. In contrast, apoptosis at the lumenal surface was inversely proportional to PKC beta(II) expression in the upper tertile. These results suggest that an elevation in PKC beta(II) expression along the crypt axis in the distal colon is linked to enhancement of cell proliferation and suppression of apoptosis, predictive intermediate biomarkers of tumor development. Therefore, select dietary factors may confer protection against colon carcinogenesis in part by blocking carcinogen-induced PKC beta(II) expression.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0143-3334
pubmed:author
pubmed:issnType
Print
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1513-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10910952-Animals, pubmed-meshheading:10910952-Apoptosis, pubmed-meshheading:10910952-Azoxymethane, pubmed-meshheading:10910952-Carcinogens, pubmed-meshheading:10910952-Cell Cycle, pubmed-meshheading:10910952-Cell Division, pubmed-meshheading:10910952-Cellulose, pubmed-meshheading:10910952-Colon, pubmed-meshheading:10910952-Colonic Neoplasms, pubmed-meshheading:10910952-Corn Oil, pubmed-meshheading:10910952-Diet, pubmed-meshheading:10910952-Fatty Acids, Omega-3, pubmed-meshheading:10910952-Immunohistochemistry, pubmed-meshheading:10910952-Isoenzymes, pubmed-meshheading:10910952-Male, pubmed-meshheading:10910952-Pectins, pubmed-meshheading:10910952-Precancerous Conditions, pubmed-meshheading:10910952-Protein Kinase C, pubmed-meshheading:10910952-Rats, pubmed-meshheading:10910952-Rats, Sprague-Dawley, pubmed-meshheading:10910952-Subcellular Fractions
pubmed:year
2000
pubmed:articleTitle
Morphodensitometric analysis of protein kinase C beta(II) expression in rat colon: modulation by diet and relation to in situ cell proliferation and apoptosis.
pubmed:affiliation
Molecular and Cell Biology Section, Faculty of Nutrition and Department of Statistics, Texas A&M University, College Station, TX 77843, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.