CILJ ISTRAŽIVANJA: Utvrditi postojanje dediferencijacije urotelnih stanica kroz aktivaciju Yamanakijevih faktora (čimbenika indukcije matičnih stanica) tijekom nastanka tumora mokraćnog mjehura u miša. MATERIJALI I METODE: Eksperimentalno istraživanje provedeno je na Katedri za imunologiju i medicinsku genetiku Medicinskog fakulteta u Splitu. Napravljene su dvije skupa od 8 miševa, kontrolna i eksperimentalna, a eksperimentalna skupina podvrgnuta je akutnom tretmanu, u trajanju od 2 tjedna, korištenjem kemikalije N-butil-N-(4-hidroksibutil)-nitrozamin (BBN) u vodi za piće u koncentraciji od 0,05% sa svrhom indukcije tumora mokraćnog mjehura. Nakon tretmana miševi su žrtvovani. Iz izolirane RNA zdravog i bolesnog tkiva napravljena je cDNA koja je zatim analizirana Q-PCR (kvantitativna lančana reakcije polimeraze) metodom. REZULTATI: Gen Sox2 pokazuje statistički značajno manji izražaj za 4,7 puta (P= 0,003). Gen Nanog nije pokazao značajnu promjenu u izražaju u tumorski promjenjenom tkivu mjehura. Gen Klf4 pokazuje statistički značajan veći izražaj u tumorskom tkivu za 5,6 puta (P< 0,001). ZAKLJUČAK: Smanjenje izražaja Sox2 gena ukazuje na potrebu za daljnjim istraživanjem međudjelovanja Yamanakijevih faktora, dok porast izražaja Klf4 gena sugerira dediferencijaciju urotelnih stanica i nastajanje karcinomskih matičnih stanica u tumorima mokraćnog mjehura.

AIM: To determine process of dedifferentiation of urothelial cells through activation of Yamanaka factors (factors of stem cell induction) during the occurence of bladder cancers in mice. MATHERIALS AND METHODS: Experimental research was conducted at Department of Immunology and Medical Genetics, University of Split School of Medicine. Two study groups were created, the control group and the experimental group which consisted of 8 mice each. The experimental group had undergone an acute treatment, 2 weeks in duration, using the chemical compound N-Butyl-N-(4-hydroxybutyl) nitrosamine (BBN) in drinking water at a concentration of 0,05% in order to induce bladder cancer development. After the treatment the mice were sacrificed. Out of the isolated RNA of both, healthy and diseased mice tissue, cDNA was synthesised and analyzed with a Q-PCR (quantitative Polimerase Chain Reaction). RESULTS: A 4,7 fold statistically significant decrease was observed in Sox2 gene expression (P= 0,003). No significant change in expression of Nanog gene was observed. A 5,6 fold statistically significant increase was observed in Klf4 gene (P< 0,001). CONCLUSION: The decrease of Sox2 expression unveils the need for further studying of Yamanaka factors interaction during bladder cancer development. The increase of Klf4 expression suggests presence of the process of dedifferentiation and possible egzistence of cancer stem cells in bladder cancer.