Abstract 904: Hypoxic attenuation of ΔB-Raf-induced senescence

Abstract

Abstract Oncogene-induced senescence (OIS) is natural surveillance mechanisms against tumorigenesis. The in-vivo oxygen concentration around tumor microenvironment has been estimated as 3%~0.5%. We investigate the effects of physiological hypoxia (1.5% O2) and pathological hypoxia (<0.5% O2) on OIS. Expression of active ΔB-Raf in human lung fibroblast IMR90 cells triggered senescence processes such as activation of senescence associated-β-galactosidase (SA-β-gal) and senescence associated heterochromatin foci (SAHF). We found that hypoxic condition delayed onset of activation of SA-β-gal. Furthermore hypoxic condition blocked formation of heterochromatin foci which was identified as a hallmark of OIS with increase of histone methylation. Rearrangement of chromatin organization by activated ΔB-Raf was also inhibited under hypoxic condition. This study shows that tumor hypoxia assists the transformed cells to overcome an obstacle of senescence caused by oncogenes. [This study was supported by the National Research Foundation of Korea (NRF), grant 2016R1A2B4012840 and 2018R1A4A1025985] Citation Format: Soojeong Chang, Hyunsung Park. Hypoxic attenuation of ΔB-Raf-induced senescence [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 904.