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Involvement of PTCH and entire signaling pathway Hedgehog/Patched in pathogenesis of ovarian tumors and malformations

The mechanism by which activation of the Hedgehog/Patched pathway leads to carcinogenesis is 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 suporting the two-hit hypothesis, was also found in non-malignant malformations (cysts), so dermoids were used in this study as representative of malformations in which mutations of PTCH and aberrations of the Hedgehog /Patched signaling might occur.The levels of expression of particular genes of the pathway were determined from extracted RNA which was previously reversally transcribed into cDNA. 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 increased synthesis found in some samples can be attributed to the pathway 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 GLI activity.

tumor suppresors; PTCH; cancer; development

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