TAILIEUCHUNG - Báo cáo khoa học: Knockdown of integrin b4-induced autophagic cell death associated with P53 in A549 lung adenocarcinoma cells

Integrin b4 is a tissue-specific protein, but its role in autophagy of lung adenocarcinoma cells is not clear. In this study, we used microtubule-associated protein 1 light chain 3 processing and acridine orange staining to reveal that knockdown of integrin b4 by its specific siRNA induced autophagic cell death in A549 lung cancer cells. | ỊFEBS Journal Knockdown of integrin b4-induced autophagic cell death associated with P53 in A549 lung adenocarcinoma cells Qiuxia He1 Bin Huang1 Jing Zhao1 Yun Zhang2 Shangli Zhang1 and Junying Miao1 2 1 Institute of DevelopmentalBiology Schoolof Life Science Shandong University China 2 The Key Laboratory of Cardiovascular Remodeling and Function Research Chinese Ministry of Education and Chinese Ministry of Health Shandong University Qilu Hospital China Keywords autophagy A549 lung cancer cells H322 lung cancer cells integrin p4 p53 protein Correspondence J. Miao School of Life Science Shandong University 27 Shanda Nan Road Jinan 250100 China Fax 86 531 88565610 Tel 86 531 88364929 E-mail miaojy@ These authors contributed equally to this work Received 18 July 2008 revised 19 September 2008 accepted 22 September 2008 Integrin P4 is a tissue-specific protein but its role in autophagy of lung adenocarcinoma cells is not clear. In this study we used microtubule-associated protein 1 light chain 3 processing and acridine orange staining to reveal that knockdown of integrin b4 by its specific siRNA induced autophagic cell death in A549 lung cancer cells. Next we investigated the effects of siRNA-mediated downregulation of integrin b4 on cell death and the level of p53. The proportion of dead cells and level of p53 were significantly increased. Inhibition of autophagy by the inhibitor 3-methyladenine attenuated the cell death induced by integrin b4 knockdown. To further understand the relationship between p53 and integrin b4 in autophagic cell death we inhibited the expression of integrin b4 by its specific siRNA in p53-mutated H322 lung cancer cells. Knockdown of integrin b4 could not induce autophagic cell death in H322 cells. The data suggest that integrin b4 is implicated in and associated with p53 in autophagy of lung cancer cells. doi Integrin b4 originally identified as a tumor-associated antigen 1 is expressed primarily .

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