Diet and colon cancer – mechanistic approach with the ApcMin/+ mous

We have used ApcMin/+ mice to study the effects of food components such as fat, different fiber and lignan sources, meat, and polyphenols on tumor formation and progression and on cell signalling pathways related to colon carcinogenesis (CRC). This is the best-characterized mouse colonic neoplasia model and analogous to the human FAP syndrome.

Min (multiple intestinal neoplasia) is an autosomal dominant trait involving a nonsense mutation in codon 850 of the murine Apc gene. As in humans, the mutation predisposes heterozygotes to intestinal tumorigenesis,. In both Min/+ mice and healthy rats, different types of diet cause considerable changes in intestinal cell signalling pathways (PKC, NF-kB, b-catenin, p53 and COX-2). In the tumor tissue and also in the surrounding mucosa, changes have been seen in the levels and subcellular localizations of several cell signalling proteins (b-catenin, cyclin D1, E-cadherin, NF-kB, and p53).

We have also shown that red meat has unfavourable effects on tumor formation whereas Finnish wild berries (bilberry, lingonberry and cloudberry) prevented tumorigenesis in this animal model. The results are in line with the epidemiological evidence on the effect of red meat and plant based foods on CRC.

The research is currently focused on plant stanols and sterols and their effect on the followig signalling pathways b-catenin, cyclin D1, p53, pERK/ERK, pAkt/Akt, caveolin, and pEGFR/EGFR. Furthermore, the effect of Western-type diet (hig in fat and low in Ca, fiber and folate) and effect of energy metabolism in tumor formation in this model is underway.

The research project will produce new information on the initiation and progression of CRC and on the effects of diet and energy metabolism to cancer risk.

Principal investigator: Marja Mutanen

Members of the research team: Anne-Maria Pajari, Mikael Niku, Essi Päivärinta, Maija Marttinen, Anu Heiman-Lindh.

PhD thesis from the project:
Anne-Maria Pajari (2000). Diet and colon protein kinase C - relation to intestinal tumour development in experimental animals.

Seija Oikarinen (2005). Role of lignan sources in tumour formation in multiple intestinal neoplasia mice.

Marjo Misikangas (2007). Dietary modulation of b-catenin signalling in an experimental model of colon cancer.

Johanna Rajakangas-Tolsa (2008). Diet, cell signaling, and tumorigenesis in multiple intestinal neoplasia mice.

Essi Päivärinta, Diet, intestinal microflora, immune function and experimental colon cancer. Ongoing. 

Maija Marttinen. Effect of plant sterols on adenoma formation in the Apc-mutated Min/+ mouse. Ongoing.