Naslov
Tumor suppressors in cancer and development

Autori
Levanat, Sonja

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

Izvornik
Life Science Conference 1998 / Slovenian Physiological Society - Ljubljana, 1998, 48-48

Skup
Life Science Conference 1998

Mjesto i datum
Gozd Martuljek, Slovenija, 19.09.1998. - 24.09.1998

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
tumor suppressors; cancer; development

Sažetak
Genes involved in carcinogenesis often play a critical role in normal development and cellular regulation. The PTCH gene, a human homologue of the Drosophila segment polarity gene patched, is a tumor suppresor for Nevoid Basal Cell Carcinoma Syndrome (NBCCS) or Gorlin syndrome, and for sporadic Basocellular Carcinomas of the skin (BCCs). Genetic studies of Drosophila show that patched (PTC) is a part of the hedgehog/signalling pathway, important in determining embryonic patterning and cell fate in multiple structures of developing larvae. Human patched is mutated in both hereditarya and sporadic NBCCS and inactivation of this gene is probably necessary step for disease to develop. The aim is delineation of the biochemical pathway in which PTCH functions as a part of signalling pathway, which may lead to rational medical therapy for BCCs and possibly for other tumors, associated with NBCCS. Gorlin syndrome patients develop severe tumors and developmental defects, where the jaw cysts (keratocysts) are most often. To test the hypothesis that malformations in this syndrome might arise through a two-hit mechanism as proposed for tumor development, we searched for loss of heterozygosity in jaw dysts. We found that the cyst lining of jaws loses the normal copy of the Gorlin syndrome region while retaining the mutant copy. So far different germline mutations along the NBCCS region have been found in DNA samples from NBCCS individuals, but no significant correlation between mutation type and phenotype has been detected indicating that it is a complex gentic disorder. Last findings combined with available genetic evidence from Drosophila, support the hypothesis that PTC is receptor for Shh (sonic hedgehog) and that another transembrane protein smo (smoothened) is also involved in a hedgehog/patched signal transduction pathway.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

POVEZANOST RADA