Naslov
The role of ΔNp73α in response to genotoxic stress in normal and tumor human cells

Autori
Horvat, Anđela ; Dulić, Vjekoslav ; Zorić, Arijana ; Slade, Neda

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

Izvornik
Periodicum Biologorum, HDIR-2 Second Meeting with International Participation “From Bench to Clinic” / Levanat, Sonja ; Levačić Cvok, Mirela ; Musani, Vesna ; Car, Diana ; Osmak, Maja ; Herak Bosnar, Maja ; Slade, Neda, Stojanović, Nikolina - Zagreb : Hrvatsko prirodoslovno društvo ; IRB, 2012, 31-31

Skup
HDIR-2 Second Meeting with International Participation “From Bench to Clinic”

Mjesto i datum
Zagreb, Hrvatska, 08.11.2012. - 09.11.2012

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
p73; cell cycle; DNA damage

Sažetak
P73 gene encodes numerous protein isoforms divided into two groups according to alternative promoter usage: tumor-suppressive TAp73 isoforms whose functions partly overlap with those of wild-type p53, and potentially oncogenic ΔNp73 isoforms which inhibit wild-type p53, p63 and p73. Since ΔNp73 isoforms are often overexpressed in human tumors showing enhanced chemoresistance, they are considered as potential markers of worse prognosis. Our investigation is focused on the impact of ΔNp73α overexpression on cell cycle regulation and response to different DNA damaging agents (ICRF-193, bleomycin, γ-irradiation) in normal and tumor human cells. ΔNp73α was overexpressed in wild-type human dermal fibroblasts (HDF-WT), HDF expressing human papilloma virus HPV16-E6 oncoprotein (HDF-E6), and U2OS human osteosarcoma cell line by retroviral infection. Our video-microscopy experiments showed that in HDF-WT ΔNp73α overexpression abrogates G2 cell cycle arrest after treatment with topoisomerase II inhibitor ICRF-193. In agreement with this, we found lower p21 expression in cells with ΔNp73α compared to control ones upon ICRF-193 treatment. To explore potential role of ΔNp73α at the G2/M checkpoint, HDF-WT and HDF-E6 were synchronized at G1/S boundary and exposed to γ- irradiation (12 Gy) after release, but FACS analysis showed no significant difference between cells expressing ΔNp73α and control. FACS analysis of γ-irradiated (3 and 5 Gy) HDF-WT and U2OS cells revealed higher percentage of polyploidy in cells overexpressing ΔNp73α. Further analysis of cell cycle progression and specific DNA damage signaling pathways will help to elucidate the role of ΔNp73α in the process of oncogenesis.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

POVEZANOST RADA