Analysis of beta-Catenin/Sox2/p63 Signal Pathway in Lung Epithelial Differentiation and Tumorigenesis

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We clarified the expression of Wnt/beta-catenin signaling and related factors in lung cancers and the regulatory mechanisms between beta-catenin and Sox2 expression. Sox2 was highly expressed in small and squamous cell carcinomas, Sox9 in squamous but also in adeno and large cell carcinomas, p63 in squamous cell carcinomas, and Notch1 especially in adenocarcinomas. These data suggests their own functions in tumorigenesis or tumor progression in each lung cancer subtype. Next we established the 3D culture system of human bronchial basal cells (VA10). Using this system we clarified that BIO (GSK3 inhibitor) contributed to form cell polarity and co-stimulation of Wnt3a and EGF induced distinct extension of cells from the sphere colonies suggesting the function to accelerate cell cycling or cell division. ChIP analysis revealed that beta-catenin might not directly bind the Sox2 promoter region and downregulate Sox2 expression in other indirect way.