Abstract
Treatment success of breast cancer patients with trastuzumab alone or in combination depends not only on HER2/NEU amplification but also on PTEN and PI3K status and efficient cell death programs. In this pilot study, we found a significant association between loss of beclin 1 and HER2/NEU amplification (both on 17q21) in breast cancers. This finding was confirmed in two public copy number microarray datasets. Furthermore, there is a trend associating beclin 1 loss with TP53 mutations, PI3KCA gene gain, and PTEN mutations. Finally, the observation that beclin 1 gene loss predicted a response to trastuzumab alone or in combination with other drugs is worthy of further confirmation in larger cohorts. Our results suggest that, beclin 1 loss may contribute to genome instability and to a defective autophagy that may lead to tumoral cell death in presence of competent apoptosis or senescence pathways.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis Regulatory Proteins / genetics*
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Apoptosis Regulatory Proteins / metabolism
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Beclin-1
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism
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Breast Neoplasms / pathology
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Chromosomes, Human, Pair 17 / genetics*
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Female
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Gene Amplification*
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Humans
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Immunoenzyme Techniques
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Loss of Heterozygosity*
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Membrane Proteins / genetics*
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Membrane Proteins / metabolism
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Mutation / genetics
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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PTEN Phosphohydrolase / genetics
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PTEN Phosphohydrolase / metabolism
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Prognosis
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RNA, Messenger / genetics
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Receptor, ErbB-2 / genetics*
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Receptor, ErbB-2 / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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Apoptosis Regulatory Proteins
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BECN1 protein, human
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Beclin-1
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Membrane Proteins
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Nuclear Proteins
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PI3KCA protein, human
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RNA, Messenger
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TP53 protein, human
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Transcription Factors
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Tumor Suppressor Protein p53
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ERBB2 protein, human
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Receptor, ErbB-2
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PTEN Phosphohydrolase
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PTEN protein, human