title: Early growth response 1 regulates glucose deprivation-induced necrosis.
abstract: Necrosis is commonly found in the core region of solid tumours due to metabolic stress such as hypoxia and glucose deprivation (GD) resulting from insufficient vascularization. Necrosis promotes tumour growth and development by releasing the tumour-promoting cytokine high mobility group box 1 (HMGB1); however, the molecular mechanism underlying necrotic cell death remains largely unknown. In this study, we show that early growth response 1 (Egr-1) is induced in a reactive oxygen species (ROS)-dependent manner by GD in several cell lines such as A549, MDA-MB-231 and HepG2 cells that exhibit necrosis upon GD. We found that Egr-1 short hairpin RNA (shRNA) prevented GD-induced necrosis and HMGB1 release. Necrosis-inhibiting activity of Egr-1 shRNA was also seen in multicellular tumour spheroids (MTSs), an in vitro tumour model system. In contrast, Egr-1 overexpression appeared to make tumour cells more susceptible to GD-induced necrosis. Finally, Egr-1 shRNA suppressed the growth of MTSs. These findings demonstrate that Egr-1 is implicated in GD-induced necrosis and tumour progression.
authors.affiliation: Department of Molecular Biology, College of Natural Sciences,                     Pusan National University, Pusan 609-735, Republic of Korea.
authors.forename: Hyun Min
authors.initials: HM
authors.lastname: Jeon
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Lee
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Ju
authors.forename: Cho Hee
authors.initials: CH
authors.lastname: Kim
authors.forename: Hye Gyeong
authors.initials: HG
authors.lastname: Park
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Kang
mesh_terms: D051766:Early Growth Response Protein 1 / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005947:Glucose / Q000172:deficiency; D024243:HMGB1 Protein / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D009336:Necrosis / Q000235:genetics*; D010957:Plasmids; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018874:Spheroids, Cellular; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D024243:HMGB1 Protein; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate