Carcinogenesis, Vol 19, 253-257, Copyright © 1998 by Oxford University Press
LA Davidson, CM Aymond, YH Jiang, ND Turner, JR Lupton and RS Chapkin
We have developed a non-invasive method utilizing feces, containing
sloughed colonocytes, as a sensitive technique for detecting diagnostic
colonic biomarkers. In this study, we used the rat colon carcinogenesis
model to determine if changes in fecal protein kinase C (PKC) expression
have predictive value in monitoring the neoplastic process. Weanling rats
were injected with saline or azoxymethane (AOM) and 36 weeks later fecal
samples and mucosa were collected, poly A+ RNA isolated, and quantitative
RT-PCR performed using primers to PKC betaII and zeta. Fecal PKC betaII and
zeta mRNA levels were altered by the presence of a tumor, with
tumor-bearing animals having a 3-fold higher (P < 0.05) PKC betaII
expression as compared with animals without tumors. In addition,
AOM-injection increased mucosal PKC betaII mRNA expression compared with
saline controls. No effect of tumor incidence on mucosal PKC betaII
expression was observed. In contrast, fecal PKC zeta expression was
2.5-fold lower (P < 0.05) in animals injected with azoxymethane versus
saline. Since tumor incidence exerts a reciprocal effect on fecal PKC
betaII and zeta mRNA expression, data were also expressed as the ratio
between PKC betaII and zeta. The isozyme ratio was strongly related to
tumor incidence, i.e. ratio for animals with tumors was 2.18 +/- 1.25,
animals without tumors was 0.50 +/- 0.16, P = 0.025. We demonstrate that
the expression of fecal PKC betaII and zeta may serve as a noninvasive
marker for development of colon tumors. A sensitive technique for the
detection of colon cancer is of importance since early diagnosis can
substantially reduce mortality.
ARTICLES
Non-invasive detection of fecal protein kinase C betaII and zeta messenger RNA: putative biomarkers for colon cancer
Molecular and Cell Biology Group, Faculty of Nutrition, Texas A&M University, College Station 77843-2471, USA.
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