1. Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression
- Author
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Kenneth Hon Kim Ban, Roberto Rangel, Luxmanan Selvanesan, Michael B. Mann, Jerrold M. Ward, Justin Y. Newberg, Alistair G. Rust, Takahiro Kodama, Liliana Guzman-Rojas, Kuan Yew Chin, Neal G. Copeland, Leslie A. McNoe, Nancy A. Jenkins, Michael A. Black, and Song Choon Lee
- Subjects
0301 basic medicine ,Lung Neoplasms ,Mutant ,Mutation, Missense ,Gene Expression ,Mice, Transgenic ,Triple Negative Breast Neoplasms ,Kaplan-Meier Estimate ,Adenocarcinoma ,Metastasis ,law.invention ,03 medical and health sciences ,Breast cancer ,law ,Cell Line, Tumor ,medicine ,Animals ,Humans ,PTEN ,Tensin ,Genes, Tumor Suppressor ,Gene ,Proportional Hazards Models ,Genetics ,Multidisciplinary ,biology ,PTEN Phosphohydrolase ,Mammary Neoplasms, Experimental ,medicine.disease ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,030104 developmental biology ,PNAS Plus ,Mutagenesis ,DNA Transposable Elements ,Disease Progression ,biology.protein ,Suppressor ,Female ,Transposon mutagenesis ,Proto-Oncogene Proteins c-fos ,Genes, Neoplasm ,Transcription Factors - Abstract
SignificanceTriple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Despite extensive cancer genome-sequencing efforts, there is still an incomplete understanding of the genetic networks driving TNBC. Here, we usedSleeping Beautytransposon mutagenesis to identify genes that cooperate with mutantPtenin the induction of TNBC. We identified 12 candidate TNBC trunk drivers and a larger number of progression genes. Subsequent functional validation studies identified eight human TNBC tumor suppressor genes, including the GATA-like transcriptional repressorTRPS1, which was shown to inhibit lung metastasis by deregulating the expression of multiple serpin and epithelial-to-mesenchymal transition (EMT) pathway genes. Our study provides a better understanding of the genetic forces driving TNBC and discovered genes with clinical importance in TNBC.
- Published
- 2016
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