engleski

Hedgehog-Gli signaling pathway in the primary cilia in benign ovarian tumors

Hedgehog-Gli (Hh-Gli) signaling pathway is involved in embryonic development, and its malfunctioning is often associated with tumorigenesis and developmental malformations. The signal transduction begins with binding of the ligand protein Sonic Hedhegog (Shh) to the transmembrane receptor Patched (Ptch). Ptch then releases its inhibition of Smoothened (Smo), which leads to activation of transcription factor Gli1 and transcription of target genes, which include Cyclin D, Cyclin E, members of Wnt and TGFβ signaling pathways, and Ptch. Ovarian dermoid cysts (DC) are benign tumors descending from germinal cells and can be derived from any of the three germinal layers. Hh-Gli has been associated with ovarian carcinoma, but its role in benign tumors is still under investigation. We developed a primary cell culture from ovarian dermoid tissue and separated several clone lines from the sample. Cells were treated with the pathway inhibitor cyclopamine, inactive analogue tomatidine or Shh protein, which activates signal transduction. RNA and protein expression of Ptch, Smo and Gli1 was detected in all clone lines. Immunofluorescent staining of primary cells showed changes in protein localization before and after treatment, confirming that Hh-Gli pathway is fully functional in these cells. Also, these cells express primary cilia, where Ptch and Smo can also be detected. We show that a subset of cells within the tumor responds to pathway inhibition and induction. Since similar results were previously shown on ovarian carcinoma, we suggest Hh-Gli pathway aberration is an early event in transformation of ovarian cells, and may assist in their progression towards malignancy.

Hedgehog signaling; ovarian tumor; primary cilia

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