Here we show that the IHh signal pathway was activated in chondrosarcoma, and knocking down the expression of Gli1 attenuated the disturbed IHh signal pathway, which not only suppressed cell proliferation and promoted G2/M cell cycle arrest but also enhanced cell apoptosis by downregulating Bcl-2 and Bcl-xl expression.
We describe a gradual decrease in the expression of Patched (PTCH) and glioma-associated oncogene homologue 1 (GLI1) (both transcribed upon IHH activity), and GLI2 with increasing malignancy, suggesting that IHH signalling is inactive and PTHLH signalling is IHH independent in secondary peripheral chondrosarcomas. cDNA expression profiling and immunohistochemical studies suggest that transforming growth factor-beta (TGF-beta)-mediated proliferative signalling is active in high-grade chondrosarcomas since TGF-beta downstream targets were upregulated in these tumours.