Knockdown of integrin beta4-induced autophagic cell death associated with P53 in A549 lung adenocarcinoma cells.

Abstract

Integrin beta4 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 beta4 by its specific siRNA induced autophagic cell death in A549 lung cancer cells. Next, we investigated the effects of siRNA-mediated downregulation of integrin beta4 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 beta4 knockdown. To further understand the relationship between p53 and integrin beta4 in autophagic cell death, we inhibited the expression of integrin beta4 by its specific siRNA in p53-mutated H322 lung cancer cells. Knockdown of integrin beta4 could not induce autophagic cell death in H322 cells. The data suggest that integrin beta4 is implicated in and associated with p53 in autophagy of lung cancer cells.

• Authors: Qiuxia He, Bin Huang, Jing Zhao, Yun Zhang, Shangli Zhang, Junying Miao
• Journal: The FEBS journal (FEBS J) Vol. 275 Issue 22 Pg. 5725-32 (Nov 2008) ISSN: 1742-4658 [Electronic] England
• PMID: 18959757 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Integrin beta4
• RNA, Small Interfering
• Tumor Suppressor Protein p53

Topics

• Autophagy
• Cell Death
• Cell Line, Tumor
• Gene Silencing
• Humans
• Integrin beta4 (physiology)
• Lung Neoplasms
• RNA, Small Interfering (pharmacology)
• Tumor Suppressor Protein p53