Expression of a sonic hedgehog signal transducer, hedgehog-interacting protein, by human basal cell carcinoma

Abstract

Background: Aberrant activation of the hedgehog pathway has been identified in various human tumours, including familial and sporadic basal cell carcinomas (BCCs). It has been postulated that binding of sonic hedgehog protein (SHH) to its receptor, patched protein (PTC), releases the inhibitory effect of PTC against smoothened protein (SMO), another protein of the SHH signalling pathway. The positive SMO signalling is not downregulated in BCCs because of the mutational inactivation of PTC. Recently, hedgehog-interacting protein (HIP) was found to bind to SHH directly and attenuate SHH signalling like PTC, while its expression was induced by SHH signals. Objectives: To examine the expression patterns of HIP, SHH and PTC gene mRNA by human BCCs, in comparison with those by normal human skin and various skin tumours. Methods: We performed quantitative reverse transcriptase-polymerase chain reaction analyses with a series of samples from BCCs, other skin tumours and normal skin. Results: We found that the mRNA expression of both HIP and PTC genes was enhanced in all samples of BCCs, whereas none of the other skin tumours tested exhibited an increased level of such mRNAs as compared with normal skin. The transcription of the SHH gene, however, was at a baseline level in most BCCs. Conclusions: These results indicate that both HIP and PTC gene expression are specifically involved in the development of BCCs, and that the production of HIP is linked with the expression of the PTC gene but not the SHH gene.