Naslov
Signal transduction in tumors: HH-GLI interactions and therapeutic potential

Autori
Levanat, Sonja ; Musani, Vesna ; Čretnik, Maja ; Orešković, Slavko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
International Journal of Molecular Medicine / Spandidos, Demetrios A. - Atena : Lychnia, 2006

Skup
The 11th World Congress on Advances in Oncology and 9th International Symposium on Molecular Medicine

Mjesto i datum
Hersonissos, Grčka, 12.10.2006. - 14.10.2006

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
HH-GLI pathway; tumors; cyclopamine; patched

Sažetak
The HH-GLI signaling pathway, also known as Hh-Ptc, SHH/PTCH/SMO pathway or Hedgehog-Patched is a pathway for signal transduction from the cell membrane to the nucleus that has beeen highly conserved through evolution. The pathway has a key role in normal development and its aberrant functioning is associated with developmental malfomations and cancer. Activation of the pathway is inhibites through binding of the secreted Hedgehog ligand Hh to its membrane receptor Ptch (12-transmembrane domain protein) relieving to co-receptor Smo (another membrane protein), which was repressed by Ptch, and actiates a cascade that leads to translocation of the active form of the transcription factor Gli to the nucleus. PTCH acts as a negative regulator of Hedgehog signaling. The role of the Hh-Gli pathway in several tumors typical for Gorlin syndrome has been studied for more than a decade, but only in the last few years its involvment with an increased activity of GLI1, PTC and Hh genes has been detected in a series of tumors not related to Gorlin syndrome (lung, breast, pancreas etc.). We analyzed series of skin and ovarian tumors which are often present in NBCCS, mostly basocellular carcinomas of the skin, ovarian fibroma and ovarian dermoids, in which we found LOH of the PTCH1 locus in basocellular carcinomas or alterations of PTCH expression in one third of ovarian fibromas and dermoids. Expression analyses showed that GLI overexpression does not always coincide with PTCH, and high levels of SHH are almost regularly, especially in dermoids, accompanied by increased expression of SMO. Our recent results on different tumors (basocellular carcinoma of the skin, dermoid cysts, ovarian fibromas, lung cancer) contribute to better understanding of mechanisms and therapeutic potential of HH-GLI pathway. Those results are based on successful growth inhibition of the Hh-Gli pathway (Chen, PNAS, 2002), both in cell cultures and on animal models by cyclopamine (a herbal extract that causes cyclopia in sheep) and its analogues, which act on Smo and block its function.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA