BASAL-CELL CARCINOMA DEVELOPMENT IS ASSOCIATED WITH INDUCTION OF THE EXPRESSION OF THE TRANSCRIPTION FACTOR GLI-1

Recent work has established that activation of Hedgehog/patched signal ling plays a key role in the development of basal cell carcinomas (BCC s). In Drosophila the effects of hedgehog signalling are mediated by t he transcription factor Cubitus interruptus, which is homologous to th e mammalian Gli family of transcription factors. In order to investiga te the downstream consequences of patched gene inactivation in BCCs, w e have investigated the expression of Gli-l and Gli-3 in normal skin a nd BCCs by reverse transcription-polymerase chain reaction (RT-PCR) an d in situ hybridization. Gli-3 was found to be expressed in both norma l skin and BCCs by both RT-PCR and in situ hybridization using a Gli-3 -specific probe. Using a sensitive RT-PCR assay we were unable to dete ct Gli-l transcripts in normal skin. Gli-l was expressed in 13 of 14 B CCs examined, and in situ hybridization confirmed that the transcripts were localized to the epithelial component of the tumours. Our result s demonstrate that inactivation of the patched gene BCCs is associated with the accumulation of Gli-l transcripts. These findings suggest th at the Gli-l transcription factor plays a key role in BCC development.