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

Scientific paper - Original scientific paper

• Author: Valentina Karin‑Kujundžić
• Author: Adriana Covarrubias‑Pinto
• Author: Anita Škrtić
• Author: Semir Vranić
• Author: Ljiljana Šerman
• Author's institution: University of Zagreb; School of Medicine; (Department of Medical Biology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences

Abstract (english)

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.

• Keywords (english): Adult; Carcinoma, Ovarian Epithelial; Cystadenocarcinoma, Serous / pathology; Female; Hedgehog Proteins; Humans; Ovarian Neoplasms / pathology; Patched-1 Receptor / genetics
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: International Journal of Oncology
• Numbering: vol. 61, no. 6, 145
• p-ISSN: 1019-6439
• e-ISSN: 1791-2423
• DOI: https://doi.org/10.3892/ijo.2022.5435
• URN:NBN: urn:nbn:hr:105:532090
• Publication: 2022-10-05
• Project: Number: KK.01.1.1.01.0008; Title (english): Reproduktivna i regenerativna medicina - istraživanje novih platformi i potencijala; Leader: Ana Katušić Bojanac; Jurisdiction: Croatia
• Document URL: http://www.spandidos-publications.com/10.3892/ijo.2022.5435
• Type of resource: Text
• Access conditions: Open access
• Created on: 2023-08-23 10:29:08