Journal article
A Transposon-based Analysis Reveals RASA1 Is Involved in Triple-Negative Breast Cancer
Cancer research (Chicago, Ill.), Vol.77(6), pp.1357-1368
03/15/2017
DOI: 10.1158/0008-5472.CAN-16-1586
PMID: 28108518
Abstract
RAS genes are mutated in 20% of human tumors, but these mutations are very rare in breast cancer. Here, we used a mouse model to generate tumors upon activation of a mutagenic T2Onc2 transposon via expression of a transposase driven by the keratin K5 promoter in a p53
background. These animals mainly developed mammary tumors, most of which had transposon insertions in one of two RASGAP genes, neurofibromin1 (
) and RAS p21 protein activator (
). Immunohistochemical analysis of a collection of human breast tumors confirmed that low expression of RASA1 is frequent in basal (triple-negative) and estrogen receptor negative tumors. Bioinformatic analysis of human breast tumors in The Cancer Genome Atlas database showed that although
mutations are rare, allelic loss is frequent, particularly in basal tumors (80%) and in association with
mutation. Inactivation of
in MCF10A cells resulted in the appearance of a malignant phenotype in the context of mutated p53. Our results suggest that alterations in the Ras pathway due to the loss of negative regulators of RAS may be a common event in basal breast cancer.
.
Details
- Title: Subtitle
- A Transposon-based Analysis Reveals RASA1 Is Involved in Triple-Negative Breast Cancer
- Creators
- Cristian Suárez-Cabrera - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainRita M Quintana - Molecular Oncology Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT)/CIBERONC, Madrid, SpainAna Bravo - Department of Veterinary Clinical Sciences, Faculty of Veterinary Medicine, University of Santiago de Compostela, Lugo, SpainM Llanos Casanova - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainAngustias Page - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainJosefa P Alameda - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainJesús M Paramio - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainAlicia Maroto - Department of Pathology, 12 de Octubre University Hospital, Madrid, SpainJavier Salamanca - Department of Pathology, 12 de Octubre University Hospital, Madrid, SpainAdam J Dupuy - Department of Anatomy and Cell Biology, Roy J. & Lucille A. Carver College of Medicine, University of Iowa, Iowa City, IowaAngel Ramírez - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, SpainManuel Navarro - Biomedical Research Institute I+12, 12 de Octubre University Hospital, Madrid, Spain
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.77(6), pp.1357-1368
- DOI
- 10.1158/0008-5472.CAN-16-1586
- PMID
- 28108518
- NLM abbreviation
- Cancer Res
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- United States
- Grant note
- P30 CA086862 / NCI NIH HHS
- Language
- English
- Date published
- 03/15/2017
- Academic Unit
- Anatomy and Cell Biology; Pathology
- Record Identifier
- 9984025458702771
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