Early growth response 1 regulates glucose deprivation-induced necrosis

Jeon,Hyun  Min; Lee,Su  Yeon; Ju,Min  Kyung; Kim,Cho  Hee; Park,Hye  Gyeong; Kang,Ho  Sung

doi:10.3892/or.2012.2134

Early growth response 1 regulates glucose deprivation-induced necrosis

Authors:
- Hyun Min Jeon
- Su Yeon Lee
- Min Kyung Ju
- Cho Hee Kim
- Hye Gyeong Park
- Ho Sung Kang
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Affiliations: Department of Molecular Biology, College of Natural Sciences, Pusan National University, Pusan 609-735, Republic of Korea, Nanobiotechnology Center, Pusan National University, Pusan 609-735, Republic of Korea
Published online on: November 14, 2012 https://doi.org/10.3892/or.2012.2134
Pages: 669-675

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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.

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