Naslov
Hedgehog signaling in prostate cancer androgen (in)dependence

Autori
Trnski, Diana ; Sabol, Maja ; Ozretić, Petar ; Musani, Vesna ; Rinčić, Nikolina ; Štefanac, Ivan ; Mrčela, Milanka ; Levanat, Sonja

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

Izvornik
HDBMB2019 Crossroads in Life Sciences / Katalinić, Maja ; Dulić, Morana ; Stuparević, Igor - Zagreb : Hrvatsko Društvo za Biotehnologiju, 2019, 131-131

ISBN
978-953-95551-7-5

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology "Crossroads in Life Sciences" (HDBMB2019)

Mjesto i datum
Lovran, Hrvatska, 25.09.2019. - 28.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
prostate cancer ; androgen ; resistance ; GLI ; GANT-61

Sažetak
Prostate cancer is the second most frequently diagnosed cancer type in men. It starts as an androgen-dependent disease, therefore, androgen deprivation presents the main treatment option for advanced stages of the disease. This type of therapy is efficient at first, but resistance and androgen independence develop quickly. Since the molecular mechanisms involved in sustaining androgen-independent growth are not fully understood, further research is needed to identify new potential therapeutic targets. Recent research indicates that the Hedgehog-GLI (HH-GLI) signaling pathway could be a key player in prostate cancer development of resistance to therapy. This pathway is primarily associated with embryonic development of many tissues and organs, but in the last two decades its role in cancer has become intensely studied. The aim of this study was to investigate the role of HH-GLI signaling in the development of androgen independence of previously androgen-dependent prostate cancer cells (LNCaP). We examined the activity of this pathway after short-term (5 days) and long- term androgen deprivation (8 months), when these cells develop androgen independence. After short-term androgen deprivation LNCaP cells display a downregulation in HH-GLI signaling and become insensitive the the GLI1/2 inhibitor GANT-61. However, after developing androgen independence GLI2 becomes upregulated and GLI3 processing into its repressor form is inhibited, indicating a role for these proteins in maintaining long-term androgen-independent growth. On the other hand, cyclopamine, an inhibitor that acts upstream of GLI, decreases the proliferation rate of LNCaP cells in the presence of androgen as well as after short- and long-term androgen deprivation, but with different effects on HH-GLI signaling activity. Our results show that canonical HH-GLI signaling is present in androgen-dependent LNCaP cells, but changes in its activity occur after short- and long-term androgen deprivation indicating a role for GLI2 and GLI3 activator forms in sustaining long-term androgen-independent growth.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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