The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of Patched

Sabol,Maja; Car,Diana; Musani,Vesna; Ozretic,Petar; Oreskovic,Slavko; Weber,Igor; Levanat,Sonja

doi:10.3892/ijo.2012.1554

The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of Patched

Authors:
- Maja Sabol
- Diana Car
- Vesna Musani
- Petar Ozretic
- Slavko Oreskovic
- Igor Weber
- Sonja Levanat
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Affiliations: Division of Molecular Medicine, Rudjer Boskovic Institute, 10002 Zagreb, Croatia, Department of Obstetrics and Gynecology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia, Division of Molecular Biology, Rudjer Boskovic Institute, 10002 Zagreb, Croatia
Published online on: July 13, 2012 https://doi.org/10.3892/ijo.2012.1554
Pages: 1411-1418

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Abstract

The Hedgehog-Gli (Hh-Gli) signaling pathway was examined in ovarian dermoids, which show characteristics of both tumors and developmental malformations. Dermoids are classified as mature teratomas that present differentiation into various tissues, mostly epidermal elements such as glands, multilayered epithelium, hair follicles and occasionally bone and cartilage. Their development is attributed to aberrant meiosis of germinal cells within the ovary. We showed activation of the Hh-Gli signaling in ovarian dermoid primary cultures. Cyclopamine treatment slows down cell proliferation, while the Sonic Hedgehog (Shh) protein stimulates cell proliferation and induces internalization of the Patched (Ptch) protein, which accumulates in the form of granules in the cytoplasm, colocalized with the Shh protein. Cyclopamine treatment decreases Gli1 localization in the nucleus compared to non-treated cells. Based on our observations, the mechanism of Hedgehog activation in the ovarian dermoids could be the ligand-dependent autocrine pathway, which can also be stimulated by paracrine signals.

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