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Monitoring autophagy in glioblastoma with antibody against isoform B of human microtubule-associated protein 1 light chain 3
Authors:Aoki Hiroshi  Kondo Yasuko  Aldape Kenneth  Yamamoto Akitsugu  Iwado Eiji  Yokoyama Tomohisa  Hollingsworth E Faith  Kobayashi Ryuji  Hess Kenneth  Shinojima Naoki  Shingu Takashi  Tamada Yutaka  Zhang Li  Conrad Charles  Bogler Oliver  Mills Gordon  Sawaya Raymond  Kondo Seiji
Institution:Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Abstract:Autophagy, an evolutionarily conserved response to stress, has recently been implicated in cancer initiation and progression, but the detailed mechanisms and functions have not yet been fully elucidated. One major obstacle to our understanding is lack of an efficient and robust method to specifically monitor autophagic cells in cancer specimens. To identify molecular events associated with autophagy, we performed cDNA microarray analysis of autophagic glioblastoma cell lines. Based on the analysis, we raised a polyclonal antibody against isoform B of human microtubule-associated protein 1 light chain 3 (LC3B). Application of the anti-LC3B antibody revealed the presence of autophagic cells in both in vitro and in vivo settings. Of the 65 glioblastoma tissues, 31 had highly positive cytoplasmic staining of LC3B. The statistical interaction between cytoplasmic staining of LC3B and Karnofsky Performance Scale score was significant. High expression of LC3B was associated with an improved outcome for patients with poorer performance, whereas, for patients with normal performance, survival was better for patients with low staining than with high staining of LC3B. Anti-LC3B antibody provides a useful tool for monitoring the induction of autophagy in cancer cells and tissues.
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