Walker, Michael (2012)
Ph.D. thesis, University of Birmingham.
There is good evidence that high dietary calcium intake reduces the incidence of colorectal cancer. The mechanism by which calcium acts is unknown. It was hypothesised that parathyroid hormone (PTH) acts on colorectal epithelium and that calcium acts by suppressing serum PTH. Real-time PCR demonstrated expression of the PTH receptor PTHR1 in normal and neoplastic colon, indicating that the colon was sensitive to PTH. Gene expression profiling using oligo-nucleotide micro-arrays was performed to identify genes;
a) Differentially expressed in response to PTH in an in-vitro model of the colorectal epithelium.
b) For which expression in normal rectal mucosa correlated with serum PTH level.
c) Differentially expressed in normal rectal mucosa in response to modulating PTH by dietary calcium supplementation.
A common finding of all three studies was regulation of the wnt signalling pathway by PTH. In the in-vivo studies, expression of genetic markers of differentiation was negatively correlated with PTH. Calcium supplementation resulted in increased expression of genetic markers of differentiation. This suggests PTH inhibits differentiation and that calcium by suppressing PTH promotes differentiation. There was also significant overlap between the genes changed by calcium, those negatively correlated with PTH and those changed by PTH in-vitro. These findings provide support for the stated hypotheses.
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