Dietary modulation of β-catenin signalling in an experimental model of colon cancer

Colorectal cancer is among the major cancers and one of the leading causes of cancer-related deaths in Western societies. Its occurrence is strongly affected by environmental factors such as diet. Thus, for preventative strategies it is vitally important to understand the mechanisms that stimulate adenoma growth and development towards accelerated malignancy or, in contrast, attenuate them to remain in quiescence for periods as long as decades. The main objective of this study was to investigate whether diet is able to modulate β-catenin signalling related to the promotion or prevention of intestinal tumourigenesis in an animal model of colon cancer, the Min/+ mouse. A series of dietary experiments with Min/+ mice were performed where fructo-oligosaccharide inulin was used for tumour promotion and four berries, bilberry (Vaccinium myrtillus), lingonberry (Vaccinium vitis-idaea), cloudberry (Rubus chamaemorus) and white currant (Ribes x pallidum), were used for tumour prevention. The adenomas (Apc-/-) and surrounding normal-appearing mucosa (Apc+/-) were investigated separately due to their mutational and functional differences. Tumour promotive and preventive diets had opposite effects on β-catenin signalling in the adenomas that was related to the different adenoma growth effects of dietary inulin and berries. The levels of nuclear β-catenin and cyclin D1 combined with size of the adenomas in the treatment groups suggests that diets induced differences in the cancerous process. Adenomas progressing to malignant carcinomas are most likely found in the sub-groups having the highest levels of β-catenin. On the other hand, adenomas staying quiescent for a long period of time are most probably found in the cloudberry or white currant diet groups. The levels of membranous E-cadherin and β-catenin increased as the adenomas in the inulin diet group grew, which could be a result of the overall increase in the protein levels of the cell. Therefore, the increasing levels of membranous β-catenin in Min/+ mice adenomas would be undesirable, due to the simultaneous increase in oncogenic nuclear β-catenin. We propose that the decreased amount of membranous β-catenin in benign adenomas of berry groups also means a decrease in the nuclear pool of β-catenin. Tumour promotion, but not the tumour prevention, influenced β-catenin signalling already in the normal appearing mucosa. Inulin-induced tumour promotion was related to β-catenin signalling in Min/+ mice, and in WT mice changes were also visible. The preventative effects of berries in the initiation phase were not mediated by β-catenin signalling. Our results suggest that, in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should be considered when evaluating preventative dietary strategies.

Kristallivalheita : Itsepetos filosofisen tulkinnan lähtökohtana eräissä draaman klassikoissa

The philosophical problem of self-deception focuses the relation between desire, advantage, evidence and harm. A self-deceptive person is irrational because he or she belives or wants to belive contrary to the available evidence. The study focuses on different forms of self-deception that come out in certain classical Western dramas. The first self-deception forms are: "S knows that ~p but still belives that p because he wants that ~p", "S wants that p and therefore belives that p.", "S belives that p against evidence t because he wants to belive that p.", "S belives that p if t but S would belive that p even if ~t because S wants to belive that p.", "S belives that p (even if there is t that ~p) because S is ignorant of it." and "S belives that p (even if there is t that ~p) because of ignorant of t due to an internal deception." The main sources on self-deception are the views of contemporary researchers of the subject, such as Robert Audi, Marcia Baron, Bas C. van Fraassen, Mark Johnston, Mike W. Martin, Brian MaLaughlin, Alfred Mele, Amélie Oksenberg Rorty, William Ruddick and Stephen L. White. In this study it is claimed that Shakespeare´s Othello presents self-deception as a tragic phenomenom from witch it follows deceptions and murders. Moliére´s Tartuffe deals with a phony hypocrite´s attempts at cheating. Ibsen´s Wild Duck defends the necessity of vital lies. Beckett´s Waiting for Godot deals with the self-deception witch is related to the waiting of the supernatural rescuer. Miller´s The Death of a Salesman tells about a man who, while pursuing the American myth of success, winds both himself and his family into the skeins of self-deception. They are studied with a Barthesian method that emphasizes the autonomy of literary work and its interpretation independently of the author´s personal history and social conditions. Self-deception has been regarded as an immoral way of thinking or way of action. However, vital lies show the necessity or necessity of the self-deception when it brings joy and optimism to the human being and supports his or her self-esteem and does not cause a suffering or damage, either to self or others. In the study, the processual character of self-deception is brought out.