| Backgrounds:The prion protein (PrP) is well known for its conformational conversion to the pathogenic prion isoform, resulting in prion diseases. Normal host encoded PrP is expressed in a variety of tissues and cells, which suggests that normal PrP has important physiological functions. Recently, a series of stuides indicated a role of PrP in the initiation and development of tumors.APC gene is a tumor suppressor gene. Mutaions in APC gene inactivates APC protein, which leads to the alteration in cell adhesion, growth, differentiation, and proliferation. Mice carrying APCmin/+ gene spontaneously develop multiple intestinal adenomas, which is considered a good animal model to investigate the initiation and development of intestinal tumors. In this study, we explored the role of PrP on tumor initiation and development by comparing intestinal tumor initiation and development in APCmin/+ mice on wild-type or PrP null background.Methods:APCmin/+ mice were mated with PrP knockout (PrP-/-) mice to obtain the APCmin/+PrP+/- heterozygous mice. By mating APCmin/+PrP+/- heterozygous mice with each other, we constructed APCmin/+PrP+/+(PrP wild type), APCmin/+PrP+/- (PrP heterozygous) and APCmin/+PrP-/-(PrP knockout) transgenic mice. We compared the survival time, the number and size of tumors, and the pathological changes in these three types of transgenic mice. The Wnt signaling pathway was analyzed by immunohistochemistry (IHC) and immunoblot analysis.Results:By comparing with the APCmin/+PrP+/+ mice and APCmin/+PrP+/- mice, the APCmin/+PrP-/- mice survived longer and developed fewer and smaller intestinal tumors, which were statistically highly significant.Conclusion:Intestinal tumor initiation and development in APCmin/+ mice were inhibited in PrP knockout background, suggesting that PrP promotes the tumor initiation and development in APCmin/+ mice. Further studies with more tumor models are needed to verify whether this conclusion can be generalized to other tumors. |
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