Expression of β-Catenin, a Key Mediator of the WNT Signaling Pathway, in Basal Cell Carcinoma

Inactivation of the patched (PTCH) gene seems to be responsible for the genesis of basal cell carcinoma (BCC). The PTCH protein forms a complex with another membrane-bound molecule, smoothened (SMO), and is an important component in the SMO/hedgehog signaling pathway.¹ Binding of PTCH to SMO represses the SMO signaling pathway, but when hedgehog is bound to PTCH, the PTCH protein seems to undergo a conformational change that leads to activation of the SMO pathway. Activation can also occur if PTCH is inactivated by loss of heterozygosity and/or mutation. Activation of the pathway results in transcription of downstream target genes. These targets may include members of the transforming growth factor β, bone morphologic protein, and WNT protein families, as well as PTCH itself.²