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Hh-Gli signaling in ovarian carcinoma

Hh-Gli signaling is implicated in ovarian carcinoma, but its role in initiation and growth of the tumor is not well defined. We detected expression of PTCH1, SMO, GLI1, SHH , SUFU, and ß-catenin genes in ovarian carcinoma. Also Ptch, Smo, Gli1 and Shh protein expression was found, while Ptch1 was shown to be associated with FIGO stage. Also, we found correlation of Hh-Gli signaling pathway genes PTCH1, SMO and SUFU. PTCH1 was found correlated with BRCA1 and BRCA2, and BRCA1 with survivin. Primary culture of high grade ovarian cancer (gradus III) shows down regulation of PTCH1, SMO, GLI1, SUFU and ß-catenin genes with higher doses of cyclopamine (7, 5 µM). Also, proliferation of the cells was blocked 48-72 h with cyclopamine (dose response 0, 5 – 7, 5 µM) or curcumin (between 15 - 30 µM) but was increased with Shh (in doses 2, 5 - 7, 5 µM). In SKOV3 ovarian cancer cell line we detected PTCH1, SMO, GLI1, SHH , SUFU, c-Myc and ß-catenin gene expression and Ptch1, Smo, Gli1 and Shh protein expression. Proliferation of these cells was blocked with cyclopamine or curcumin (24-72 h) and addition of Shh haven’t shown increased proliferation. Gli1 transfected SKOV3 cells have higher PTCH1, SMO, GLI1, GLI2 and SUFU expression, but not GLI3. Also, siRNA PTCH down regulates PTCH1 expression. Interestingly, upon addition of Shh within 4 h, transwell cell migration assay showed an increase in migration capability of the cells, suggesting pathway activation has a role in migration, and possibly metastases. Those results might have implications in search for new molecular targets for ovarian carcinoma.

Hh-Gli signaling; ovarian carcinoma

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