Abstract：
BACKGROUND & AIMS:We recently showed that dietary supplementation with an analogue of 1alpha,25-dihydroxy-vitamin D3, 1alpha,25-dihydroxy-16-ene-23-yne-26,27 F6-vitamin D3 (RO24-5531), reduced the incidence of colonic tumors in rats treated with azoxymethane (AOM). The aim of this study was to determine whether alterations in specific isoforms of protein kinase C (PKC) are involved in this phenomenon. METHODS:Protein abundance and subcellular distribution of several PKC isoforms were examined and compared in AOM-induced tumors of rats fed control and RO24-5531-supplemented diets. RESULTS:In both AOM-induced colonic adenomas and carcinomas, a significant down-regulation of PKC-alpha, -delta, and -zeta and an up-regulation of PKC-beta11 were found compared with control colonocytes. Dietary RO24-5531 preserved the expression of PKC-zeta and increased the abundance of PKC-epsilon in carcinogen-induced adenomas. CONCLUSIONS:Because identical changes in specific isoforms of PKC were found in AOM-induced adenomas and carcinomas, these alterations may be involved in the early stage(s) of colonic malignant transformation. Moreover, the ability of RO24-5531 to block the changes in PKC-zeta induced by AOM, as well as to up-regulate PKC-epsilon, may underlie its ability to prevent adenomas from progressing to carcinomas.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Wali RK,Bissonnette M,Khare S,Aquino B,Niedziela S,Sitrin M,Brasitus TAdoi
10.1053/gast.1996.v111.pm8698190subject
Has Abstractpub_date
1996-07-01 00:00:00pages
118-26issue
1eissn
0016-5085issn
1528-0012pii
S0016508596003083journal_volume
111pub_type
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