engleski

HH-GLI interactions in different tumors and therapeutic potential

The role of the Hh-Gli pathway in several tumors typical for Gorlin syndrome has been studied for more than a decade, but only in the last few years increased activity of GLI1, PTC and HH genes has been detected in a series of tumors not related to Gorlin syndrome (lung, breast, prostate, pancreas etc.). In basocellular carcinomas of the skin, ovarian fibroma and ovarian dermoids, we often found LOH of the PTCH1 locus. Alterations of PTCH expression in those tissues did not always follow GLI overexpression but high levels of SHH are almost regularly detected, especially in dermoids accompanied by increased expression of SMO. Our recent results of methylation status on different tumors (basocellular carcinoma of the skin, dermoid cysts, ovarian fibromas) explains difference in expression of GLI 1 and PTCH according to methylated CpG regions in a PTCH promoter. Those results, along with successful tumor growth inhibition in cell cultures by cyclopamine, will contribute to better understanding of the mechanisms of Hh-Gli pathway.

Hedgehog-Gli Signaling; Cancer Cells

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