1. Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.
- Author
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Rangel R, Lee SC, Hon-Kim Ban K, Guzman-Rojas L, Mann MB, Newberg JY, Kodama T, McNoe LA, Selvanesan L, Ward JM, Rust AG, Chin KY, Black MA, Jenkins NA, and Copeland NG
- Subjects
- Adenocarcinoma secondary, Animals, Cell Line, Tumor, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Disease Progression, Female, Gene Expression, Gene Expression Regulation, Neoplastic, Genes, Neoplasm, Genes, Tumor Suppressor, Humans, Kaplan-Meier Estimate, Lung Neoplasms, Mammary Neoplasms, Experimental pathology, Mice, Transgenic, Mutagenesis, Mutation, Missense, Proportional Hazards Models, Proto-Oncogene Proteins c-fos genetics, Proto-Oncogene Proteins c-fos metabolism, Repressor Proteins, Transcription Factors genetics, Transcription Factors metabolism, Triple Negative Breast Neoplasms genetics, Triple Negative Breast Neoplasms mortality, Triple Negative Breast Neoplasms pathology, Adenocarcinoma genetics, DNA Transposable Elements, Mammary Neoplasms, Experimental genetics, PTEN Phosphohydrolase genetics
- Abstract
Triple-negative breast cancer (TNBC) has the worst prognosis of any breast cancer subtype. To better understand the genetic forces driving TNBC, we performed a transposon mutagenesis screen in a phosphatase and tensin homolog (Pten) mutant mice and identified 12 candidate trunk drivers and a much larger number of progression genes. Validation studies identified eight TNBC tumor suppressor genes, including the GATA-like transcriptional repressor TRPS1 Down-regulation of TRPS1 in TNBC cells promoted epithelial-to-mesenchymal transition (EMT) by deregulating multiple EMT pathway genes, in addition to increasing the expression of SERPINE1 and SERPINB2 and the subsequent migration, invasion, and metastasis of tumor cells. Transposon mutagenesis has thus provided a better understanding of the genetic forces driving TNBC and discovered genes with potential clinical importance in TNBC., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
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