New insight into the role of PTCH1 protein in serous ovarian carcinomas

Karin-Kujundzic,Valentina; Covarrubias-Pinto,Adriana; Skrtic,Anita; Vranic,Semir; Serman,Ljiljana

doi:10.3892/ijo.2022.5435

New insight into the role of PTCH1 protein in serous ovarian carcinomas

Authors:
- Valentina Karin-Kujundzic
- Adriana Covarrubias-Pinto
- Anita Skrtic
- Semir Vranic
- Ljiljana Serman
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Affiliations: Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia, Institute of Biochemistry II, School of Medicine, Goethe University, D‑60590 Frankfurt am Main, Germany, Centre of Excellence in Reproductive and Regenerative Medicine, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia, College of Medicine, QU Health, Qatar University, 2713 Doha, Qatar
Published online on: October 5, 2022 https://doi.org/10.3892/ijo.2022.5435
Article Number: 145
Copyright: © Karin-Kujundzic et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The Hedgehog (Hh) signaling pathway is essential for normal embryonic development, while its hyperactivation in the adult organism is associated with the development of various cancers. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. Therefore, the present study investigated the role of protein patched homolog 1 (PTCH1), a component of the Hh signaling pathway, and changes in the promoter methylation status of the corresponding gene in a cohort of low‑(LGSC) and high‑grade serous ovarian carcinomas (HGSC) and HGSC cell lines (OVCAR8 and OVSAHO). PTCH1 protein expression level was analyzed using immunohistochemistry in tissue samples and immunofluorescence and western blotting in cell lines. DNA methylation patterns of the PTCH1 gene were analyzed using methylation‑specific PCR. PTCH1 protein expression was significantly higher in HGSCs and LGSCs compared with controls (healthy ovaries and fallopian tubes). Similarly, ovarian cancer cell lines exhibited significantly higher PTCH1 protein expression compared with a normal fallopian tube non‑ciliated epithelial cell line (FNE1). PTCH1 protein fragments of different molecular weights were detected in all cell lines, indicating possible proteolytic cleavage of this protein, resulting in the generation of soluble N‑terminal fragments that are translocated to the nucleus. DNA methylation of the PTCH1 gene promoter was exclusively detected in a proportion of HGSC (13.5%) but did not correlate with protein expression. PTCH1 protein was highly expressed in serous ovarian carcinoma tissues and cell lines, while PTCH1 promoter methylation was only detected in HGSC. Further investigation is required to elucidate the possible mechanisms of PTCH1 activation in serous ovarian carcinomas.

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