Prevention Of Colon Cancer And Physical Activity: Alteration Of Gene Expression In The Colon

Introduction
Epidemiological data indicate that physical activity may reduce the incidence of colon cancer of about 40-50%. There
are some supposed mechanisms to be responsible for the protection against this type of cancer. Considered biological
mechanisms are changes in immunological (e.g. prostaglandinratio, activity of immune cell), glycolytic (e.g.
circulationg IGF- or glucose-level) or apoptotic pathways (e.g. levels of proapoptotic or antiapoptotic genes) [1]. So far
studies about the mechanistical background of the influence of physical exercise are rare.

Methods
Therefore we investigated alterations of gene expression in the colon of male Wistar rats after 13 weeks of physical
activity (n=20). Computer aided running wheel cages determined voluntary physical exercise. 9 male sedentary rats
served as a control group. Blood samples were drawn after 8 and 13 weeks and IGF-1 and testosterone hormone levels
were analysed. At the end of the study we extracted the mucosa of the proximal colon. To measure the expression of
genes which are discussed to be involved in the protection mechanisms of physical activity against colon cancer we
used Real-Time PCR. Following genes were determined: IGF-1, PFK, IGF-1R, COX-2, PPARgamma, ODC-1, Bcl-2,
HIF1-alpha. As house keeping genes we use 18S, aldolase A and GAPDH.

Results
We measured voluntary running behaviour from 1168+880m up to 10766+3869m per night. Plasma IGF-1 level was
significant lower in the training group (13 weeks:1370+257 ng/ml)compared to the control group (13 weeks: 2039+218
ng/ml). The testosterone data tend to decrease in the training group at the end of the study (from 5.49+3,37 ng/ml to
3,07+1,51 ng/ml. The Real-time PCR analysis showed no long-term effects in the gen regulation of COX-2, IGF-1,
ODC-1, Bcl-2, PPAR-gamma and HIF1-alpha in the colon. Correlations between the blood hormone level and their
some of their target genes could not be detected. Interestingly, the house keeping gene 18S seems to be regulated!

Discussion / Conclusions
In summary our present data do not confirm the supposed mechanisms in the prevention of colon cancer. Changes
in the hormone plasma level do not correlate with the expression of the appropriate gene in the colon mucosa. In
contrast to literature [3] our results indicate that 18S rRNA is not reliable as an internal control for colon tissue of
trained versus untrained rats. Further investigations have to verify this results.

References
[1]. Friedenreich CM, Orenstein MR (2002), J Nutr., 132(11 Suppl): 3456-64
[2]. Hoffmann-Goetz L. (2003). Med Sci Sports Exerc., 35(11): 1828-33
[3]. Tsuji N et al. (2002). Anticancer Res., 22(6C): 4173-8

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