The role of Wnt and Shh signaling systems in noggin-induced tumorigenesis

Abstract

The cross-interaction between BMP, Wnt and Shh signalling pathways in developing epithelial skin tumours remains poorly understood. To study the role of Wnt and Shh signalling pathways in tumour development upon BMP inhibition, we utilized a transgenic mouse model, overexpressing BMP antagonist noggin in the skin epithelium and leading to the development of hair follicle-derived tumours shortly after birth. Comparative gene and protein expression analyses revealed up-regulation of Wnt and Shh signalling systems in the skin of transgenic mice at various stages of follicular tumour development. Furthermore, recombinant BMP-4 suppresses the expression of Shh in the culture of tumor cells, while pharmacological inhibitors of Wnt and Shh significantly slow down the formation and development of tumors in noggin-expressing transgenic mice. These results enhance our knowledge about the role of growth factors in carcinogenesis and may lead to finding new targets for specific therapies for oncological diseases.

Keywords

• signaling pathways of bmp
• noggin
• tumors
• skin
• transgenic mice