Expression of sonic hedgehog signal transducers, patched and smoothened, in human basal cell carcinoma

In basal cell nevus syndrome (BCNS) patients, mutations of a gene, patched (ptc), which encodes a putative signal transducer of sonic hedgehog protein (SHH), were found and are thought to be one of the major causes of BCNS. T he SHH signaling pathway is an important developmental pathway, and ptc pro tein (PTC) is a suppressive component serving as a receptor for the secrete d SHH. Another transmembrane protein, smoothened (SMO), forms a complex wit h PTC and regulates this signaling pathway. Recent transgenic studies have strengthened the importance of the SHH signaling system in the etiology of basal cell carcinoma (BCC), In this study, we examined the expression patte rns of mRNA for ptc and smo in two different BCC subtypes and normal skin. We found that the expressions of ptc and smo mRNA were enhanced in the tumo r nests of the nodular BCC, especially at the advancing portions, but were under the detectable level in the superficial BCC cases examined, indicatin g that ptc and smo mRNA expressions might be associated with BCC tumor prog ression and divide the BCC histologic types into two subtypes, superficial and nodular types. In addition, no obvious signals for ptc and smo mRNA wer e detected in the normal human epidermis, appendages, or seborrheic keratos is, indicating that the abnormal proliferation of follicular epithelial cel ls caused by ptc, smo and/or other genetic changes, which also cause ptc an d smo overexpressions, might result in BCC tumor formation.