Interactions and therapeutic potential of Hedgehog-Gli signaling pathway genes in ovarian tumors (CROSBI ID 561716)
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Podaci o odgovornosti
Levanat, Sonja ; Cretnik, Maja ; Musani, Vesna ; Oreskovic, Slavko
engleski
Interactions and therapeutic potential of Hedgehog-Gli signaling pathway genes in ovarian tumors
The Hh-Gli signaling pathway known as Hh-Ptc or Hh/Ptc/Smo plays a major role in embryonic development and deregulated cause developmental malformations and tumorigenesis. The pathway involvement in breast, lung, prostate, digestive tract and other tumors becoming apparent recently. Normally secreted protein Hh (Hedgehog) binds to a transmembrane protein Ptc (Patched), releasing repression of Smo (Smoothened), a membrane protein, triggering a signaling cascade within the cell, finally causing expression of target genes, a tracriptional factor Gli, onvolved in cell proliferation , PTCH itself, which limits, and finally blocks the pathway, and many others. Recent findings suggest two hypothetical models of abnormal Hh-Gli pathway activation. One model (on basocellular carcinomas of ther skin (BCCs) and ovarian fibroma), suggests constitutive activation of the pathway within the cell, and doesnot require outside stimulation. The other on lung and breast tumors suggest abnormal Hh stimulation from the surrounding cells, whichcauses a strong intracellular response of the pathway. We analyzed the pathway activation on human tumors:dermoids (develop from embryonic stem cells ; they show elements of both developmental malformations and tumors) and ovarian carcinomas, by blocking and reactivating the pathway. In dermoids we showed also the role of its haploinsufficiency, while in ovarian carcinomas inactivation of the PTCH gene is mostly a consequence of deletions in first ten exons. Also, interactions with other pathways as WNT pathway are related to some extend in borderline ovarian tumors.
signaling pathway Hh-Gli ; cancer
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Podaci o prilogu
68-68.
2009.
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objavljeno
Podaci o matičnoj publikaciji
The FEBS journal
Perham, Richard
Oxford: Wiley-Blackwell
1742-464X
1742-4658
Podaci o skupu
34th FEBS Congress
poster
04.07.2009-09.07.2009
Prag, Češka Republika
Povezanost rada
Temeljne medicinske znanosti