Abstract
DNA repair is one of the major causes of spontaneous drug and radiation resistance in patients with lung adenocarcinomas (LADC). 53BP1 is a mediator that relays signals from DNA damage sensors and activates various effectors for the DNA repair and cell survival. In this study we investigated the clinical and biological significance of 53BP1. Expression of 53BP1 was detected by immunoblotting and immunohistochemistry. Our data showed that 53BP1 was detected in 166 (75.8%) of 219 LADC patients. Expression of 53BP1 correlated with tumor stage, cigarette smoking, lymphovascular invasion and poor clinical outcome. In vitro, increased 53BP1 expression elevated drug resistance, and silencing of 53BP1 expression reduced cisplatin resistance. Our results suggest that 53BP1 expression plays an important role in cisplatin resistance and predicts the prognosis for LADC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy
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Adenocarcinoma / genetics*
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Aged
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Animals
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Biomarkers, Pharmacological / metabolism
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Biomarkers, Tumor / genetics
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Biomarkers, Tumor / metabolism
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Cisplatin / pharmacology
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Cisplatin / therapeutic use*
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Drug Resistance, Neoplasm / genetics*
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Female
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Intracellular Signaling Peptides and Proteins / genetics*
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Intracellular Signaling Peptides and Proteins / metabolism
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Intracellular Signaling Peptides and Proteins / physiology
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Lung Neoplasms / drug therapy
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Lung Neoplasms / genetics*
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Male
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Mice
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Mice, Inbred BALB C
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Middle Aged
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Tumor Cells, Cultured
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Tumor Suppressor p53-Binding Protein 1
Substances
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Antineoplastic Agents
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Biomarkers, Pharmacological
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Biomarkers, Tumor
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Intracellular Signaling Peptides and Proteins
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TP53BP1 protein, human
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Tumor Suppressor p53-Binding Protein 1
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Cisplatin