Oncotarget, 2016-05, Vol.7 (21), p.31014-31028
2016
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- Autor(en) / Beteiligte
- Titel
- Growth suppression by MYC inhibition in small cell lung cancer cells with TP53 and RB1 inactivation
- Ist Teil von
- Oncotarget, 2016-05, Vol.7 (21), p.31014-31028
- Ort / Verlag
- United States: Impact Journals LLC
- Erscheinungsjahr
- 2016
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Small cell lung cancer (SCLC) is the most aggressive type of lung cancer with high mortality. One of the MYC family genes, MYC, MYCL or MYCN, is amplified in ~20% of the SCLCs; therefore, MYC proteins are potential therapeutic targets in SCLC patients. We investigated the therapeutic impact of Omomyc, a MYC dominant negative, in a panel of SCLC cell lines. Strikingly, Omomyc suppressed the growth of all tested cell lines by inducing cell cycle arrest and/or apoptosis. Induction of G1 arrest by Omomyc was found to be dependent on the activation of CDKN1A, in part, through the TP73 pathway. Our results strongly indicate that SCLC cells carrying amplification of MYC, MYCL or MYCN are addicted to MYC function, suggesting that MYC targeting would be an efficient therapeutic option for SCLC patients.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1949-2553eISSN: 1949-2553DOI: 10.18632/oncotarget.8826Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5058735
- Format
- –
- Schlagworte
- Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - genetics, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors - metabolism, Cell Cycle Checkpoints - genetics, Cell Death - genetics, Cell Growth Processes - genetics, Gene Amplification, Gene Silencing, Genes, p53, Genetic Therapy - methods, HEK293 Cells, Humans, Lung Neoplasms - genetics, Lung Neoplasms - metabolism, Lung Neoplasms - pathology, Lung Neoplasms - therapy, Molecular Targeted Therapy, Peptide Fragments - biosynthesis, Peptide Fragments - genetics, Proto-Oncogene Proteins c-myc - antagonists & inhibitors, Proto-Oncogene Proteins c-myc - biosynthesis, Proto-Oncogene Proteins c-myc - genetics, Research Paper, Retinoblastoma Binding Proteins - genetics, Retinoblastoma Binding Proteins - metabolism, Small Cell Lung Carcinoma - genetics, Small Cell Lung Carcinoma - metabolism, Small Cell Lung Carcinoma - pathology, Small Cell Lung Carcinoma - therapy, Transfection, Tumor Cells, Cultured, Tumor Suppressor Protein p53 - genetics, Tumor Suppressor Protein p53 - metabolism, Ubiquitin-Protein Ligases - genetics, Ubiquitin-Protein Ligases - metabolism