engleski

Hh-Gli signaling pathway activity in breast cancer cell lines

Hedgehog-Gli (Hh-Gli) signaling pathway is involved in embryonic development, and its malfunctioning is often associated with tumorigenesis and developmental malformations. The entire pathway is still not completely elucidated. It begins with binding of the ligand protein Sonic Hedhegog (Shh) to the transmembrane receptor Patched (Ptc). Ptc then releases its inhibition of Smoothened (Smo), and a cytoplasmatic cascade of phosphorylation and dephorsphorylation events leads to activation of transcription factor Gli and transcription of target genes, which include Cyclin D, Cyclin E, members of Wnt and TGF-beta signaling pathways, and Ptc itself. In this work we focus our interest on human breast cancer cell lines MCF7 and Sk-Br-3 where we intend to see if Hh-Gli signaling pathway is aberrantly expressed and if it is ligand dependent. Also, we are interested in potential therapeutical application of a known pathway inhibitor cyclopamine, whose activity we intend to test on these cells. Real-Time PCR demonstrated variable expression of the Hh-Gli pathway genes (SHH, PTCH, GLI1, SMO and SUFU). We also tested some pathway related genes p16, c-myc and beta-catenin. Western blot analysis shows difference in protein expression of main members of the pathway (Ptch, Smo, Shh and Gli1). Our preliminary results suggest Hh-Gli pathway involvement in tumorigenesis in tested cancer cell lines with variable intensity. Those results gave a promising models for further studies.

Hh-Gli signaling pathway ; breast cancer cell lines ; cyclopamine

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