例如:"lncRNA", "apoptosis", "WRKY"

CHUK/IKK-α loss in lung epithelial cells enhances NSCLC growth associated with HIF up-regulation.

Life Sci Alliance. 2019 Dec 02;2(6)
Evangelia Chavdoula 1 , David M Habiel 2 , Eugenia Roupakia 1 , Georgios S Markopoulos 1 , Eleni Vasilaki 3 , Antonis Kokkalis 3 , Alexander P Polyzos 3 , Haralabia Boleti 4 , Dimitris Thanos 3 , Apostolos Klinakis 3 , Evangelos Kolettas 1 , Kenneth B Marcu 5
Evangelia Chavdoula 1 , David M Habiel 2 , Eugenia Roupakia 1 , Georgios S Markopoulos 1 , Eleni Vasilaki 3 , Antonis Kokkalis 3 , Alexander P Polyzos 3 , Haralabia Boleti 4 , Dimitris Thanos 3 , Apostolos Klinakis 3 , Evangelos Kolettas 1 , Kenneth B Marcu 5
+ et al

[No authors listed]

Author information
  • 1 Biomedical Research Division, Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology, Ioannina, Greece.
  • 2 Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • 3 Biomedical Research Foundation Academy of Athens, Athens, Greece.
  • 4 Intracellular Parasitism Laboratory, Department of Microbiology and Light Microscopy Unit, Hellenic Pasteur Institute, Athens, Greece.
  • 5 Department of Biological Sciences, San Diego State University, San Diego, CA, USA.

摘要


Through the progressive accumulation of genetic and epigenetic alterations in cellular physiology, non-small-cell lung cancer (NSCLC) evolves in distinct steps involving mutually exclusive oncogenic mutations in K-Ras or EGFR along with inactivating mutations in the p53 tumor suppressor. Herein, we show two independent in vivo lung cancer models in which CHUK/IKK-α acts as a major NSCLC tumor suppressor. In a novel transgenic mouse strain, wherein IKKα ablation is induced by tamoxifen (Tmx) solely in alveolar type II (AT-II) lung epithelial cells, IKKα loss increases the number and size of lung adenomas in response to the chemical carcinogen urethane, whereas IKK-β instead acts as a tumor promoter in this same context. IKKα knockdown in three independent human NSCLC lines (independent of K-Ras or p53 status) enhances their growth as tumor xenografts in immune-compromised mice. Bioinformatics analysis of whole transcriptome profiling followed by quantitative protein and targeted gene expression validation experiments reveals that IKKα loss can result in the up-regulation of activated HIF-1-α protein to enhance NSCLC tumor growth under hypoxic conditions in vivo.