Regulation of survivin expression by the Hedgehog-GLI signaling pathway in human melanoma cell lines
Abstrakt
Survivin is a crucial antiapoptotic protein expressed in tumors whereas its expression in the majority of normal tissues is negligible. It is widely believed that transcription of the survivin gene is driven mainly by the transcription factor Sp1.
We observed that in most melanoma cell lines endogenous survivin protein level substantially decreases after the incubation with the GLI1/2 inhibitor GANT61. Further, several GLI-like consensus sites are present in the survivin promoter.
The survivin promoter-reporter likewise responds to GANT61 by the reduction of its activity by about 50%. Moreover, the promoter-reporter positively responds to the cotransfection of GLI1 expression vector.
The expression of GLI1 protein is predominantly high in tested cell lines. These data suggest that the activity survivin promoter is enhanced by the Hedgehog signaling pathway, which has been reported previously to be deregulated in melanoma.