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Transposon mutagenesis identifies genes that cooperate with mutant Pten in breast cancer progression.

Authors :
Rangel, Roberto
Guzman-Rojas, Liliana
Mann, Michael B.
Newberg, Justin Y.
Takahiro Kodama
Jenkins, Nancy A.
Copeland, Neal G.
Song-Choon Lee
Ward, Jerrold M.
Chin, Kuan-Yew
Hon-Kim Ban, Kenneth
McNoe, Leslie A.
Selvanesan, Luxmanan
Black, Michael A.
Rust, Alistair G.
Source :
Proceedings of the National Academy of Sciences of the United States of America; 11/29/2016, Vol. 113 Issue 48, pE7749-E7758, 10p
Publication Year :
2016

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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
00278424
Volume :
113
Issue :
48
Database :
Complementary Index
Journal :
Proceedings of the National Academy of Sciences of the United States of America
Publication Type :
Academic Journal
Accession number :
119933077
Full Text :
https://doi.org/10.1073/pnas.1613859113