engleski

Alterations of PTCH are atributed to Hedgehog/Patched pathway activation in ovarian fibromas and dermoids

The mechanism by which activationof the Hedgehog/Patched pathway leads to carcinogenesisis not entirely clear, but the pathway malfunctioning in some tumors has been demonstrated by mutations and /or aberrant expression of its genes. The aim of our study was to detect involvement of PTCH and of the entire signaling pathway in pathogenesis of ovarian fibroma tumors and dermoids. Loss of heterozygosity for PTCH region in those tumors supporting the two-hit hypothesis, was also found in non-malignant malformations (cysts), so dermoids were used in this tudyy as representative of malformations in which mutations of PTCH and aberrations of the Hedgehog/Patched signaling might occur. Summarily our results showed high levels of SHH almost regularly, especially in dermoids, usually accompanied by increased expression of SMO. This might indicate that the tissue is constantly exposed to SHH signaling. Alterations of PTCH indicated in one third of ovarian fibromas and dermoids exhibit LOH in the vicinity of the PTCH1 locus. PTCH is also a target gene, its increaased synthesis found in some samples can be atributed to thepathway activation. However, it is interesting that GLI overexpression does not coincide with that of PTCH, and is found only in small proportion of cases. This leads to conclusion that proliferation of these tissues is not necessarily related to the GLI activity. LOH findings in the PTCH locus, and increased expression of several genes in the Hedgehog/Patched pathway, strongly suggest that the pathway is involed in both ovarian fibroma and dermoids. Although our observation do not really clarify mechanisms of patway functioning, they may contribute to further investigations.

tumor suppressors; patched; signaling pathway

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