The Hedgehog signaling pathway in ovarian teratoma is stimulated by Sonic Hedgehog which induces internalization of Patched.
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.
Division of Molecular Medicine, Rudjer Boskovic Institute, 10002 Zagreb, Croatia.
Maja
M
Sabol
Diana
D
Car
Vesna
V
Musani
Petar
P
Ozretic
Slavko
S
Oreskovic
Igor
I
Weber
Sonja
S
Levanat
D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D003884:Dermoid Cyst / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D053823:Hedgehog Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D061251:Primary Cell Culture; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013724:Teratoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014704:Veratrum Alkaloids / Q000008:administration & dosage; D000071676:Zinc Finger Protein GLI1
C400551:GLI1 protein, human; D053823:Hedgehog Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; C509239:SHH protein, human; D014157:Transcription Factors; D014704:Veratrum Alkaloids; D000071676:Zinc Finger Protein GLI1; C000541:cyclopamine