Keratin filament networks act as supportive scaffolding within epithelial cells that allows for dissipation of mechanical stress. This function establishes keratin filament networks as the primary contributor to the structural integrity of epithelial tissues. Keratin 17 (K17) gene expressions is observed within the hair follicle, at sites of injury to the epidermis, and in hyperproliferative disease states such as psoriasis and carcinoma. Specifc patterns of keratin gene expression are associated with tissue type, level of mitotic activity, and cell motility. Cancer cells exhibit alterations in these basic cellular properties as well as modifications in keratin expression. The main objective of this proposal is to determine how intermediate filament proteins contribute to the cancer phenotype. Utilizing a transgenic mouse model for basal cell carcinoma (BCC.) and a K17 knockout line, we will assess formation and progression of BCC in the absence of K17, using histological methods, microarray analysis, and culture systems. The role of the sonic hedgehog signaling pathway, which is integral to hair follicle development and responsible for BCC formation, in the regulation of K17 gene expression will be explored. The hair phenotype in the BCC mouse model will also be characterized.
| Depianto, Daryle; Kerns, Michelle L; Dlugosz, Andrzej A et al. (2010) Keratin 17 promotes epithelial proliferation and tumor growth by polarizing the immune response in skin. Nat Genet 42:910-4 |
