Stromal PTEN determines mammary epithelial response to radiotherapy

Nature Communications
G M SizemoreM C Ostrowski

Abstract

The importance of the tumor-associated stroma in cancer progression is clear. However, it remains uncertain whether early events in the stroma are capable of initiating breast tumorigenesis. Here, we show that in the mammary glands of non-tumor bearing mice, stromal-specific phosphatase and tensin homolog (Pten) deletion invokes radiation-induced genomic instability in neighboring epithelium. In these animals, a single dose of whole-body radiation causes focal mammary lobuloalveolar hyperplasia through paracrine epidermal growth factor receptor (EGFR) activation, and EGFR inhibition abrogates these cellular changes. By analyzing human tissue, we discover that stromal PTEN is lost in a subset of normal breast samples obtained from reduction mammoplasty, and is predictive of recurrence in breast cancer patients. Combined, these data indicate that diagnostic or therapeutic chest radiation may predispose patients with decreased stromal PTEN expression to secondary breast cancer, and that prophylactic EGFR inhibition may reduce this risk.

References

Mar 29, 1992·The New England Journal of Medicine·J D BoiceJ T Flannery
Jan 14, 1988·The New England Journal of Medicine·M A TuckerS A Rosenberg
Sep 1, 1986·Journal of the National Cancer Institute·R E ShoreB Pasternack
Oct 20, 1993·Journal of the National Cancer Institute·A MattssonL E Rutqvist
Jan 6, 1993·Journal of the National Cancer Institute·S L HancockR T Hoppe
Mar 21, 1996·The New England Journal of Medicine·S BhatiaA T Meadows
Mar 17, 2001·Nature Reviews. Molecular Cell Biology·Y Yarden, M X Sliwkowski
Jul 27, 2001·Journal of Mammary Gland Biology and Neoplasia·K L Troyer, D C Lee
Aug 2, 2001·Proceedings of the National Academy of Sciences of the United States of America·A LoonstraJ Jonkers
Aug 22, 2001·Radiotherapy and Oncology : Journal of the European Society for Therapeutic Radiology and Oncology·J Unnithan, R M Macklis
Mar 22, 2003·Experimental Cell Research·Ami CitriYosef Yarden
Apr 12, 2003·The Lancet Oncology·Kenan DenizAnand Purushotham
Jul 24, 2003·JAMA : the Journal of the American Medical Association·Lois B TravisEthel Gilbert
Mar 31, 2004·Proceedings of the National Academy of Sciences of the United States of America·Charlotte KuperwasserRobert A Weinberg
Nov 19, 2004·Nature·Neil A BhowmickHarold L Moses
Feb 16, 2005·Cancer Cell·Janusz PucRamon Parsons
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 7, 2006·Nature·Mark ShackletonJane E Visvader
Mar 31, 2006·Nature Reviews. Cancer·Raghu Kalluri, Michael Zeisberg
Apr 21, 2007·Nature Reviews. Cancer·Josie Ursini-SiegelWilliam J Muller
Jun 21, 2007·Nature Immunology·Marc Schmidt-Supprian, Klaus Rajewsky
Oct 12, 2007·The New England Journal of Medicine·Daniel F HayesUNKNOWN Cancer and Leukemia Group B (CALGB) Investigators
Jan 10, 2008·Nature Biotechnology·Mazen W KaramanPatrick P Zarrinkar
Feb 5, 2008·Cancer Research·Anthony J TrimboliGustavo Leone
Feb 19, 2008·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Toshimitsu TanakaRaymond E Meyn
Feb 26, 2008·Annals of Oncology : Official Journal of the European Society for Medical Oncology·M UntchUNKNOWN HERA Study Team
Feb 11, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Joel S ParkerPhilip S Bernard
Aug 6, 2009·The Lancet Oncology·Fatiha El GhissassiUNKNOWN WHO International Agency for Research on Cancer Monograph Working Group
Oct 6, 2009·Journal of Cellular and Molecular Medicine·R G DumitrescuP G Shields
Oct 23, 2009·Nature·Anthony J TrimboliGustavo Leone
Jul 17, 2010·Journal of the National Cancer Institute·Debra L FriedmanJoseph P Neglia
Mar 8, 2011·Cell·Douglas Hanahan, Robert A Weinberg
May 20, 2011·Nature Reviews. Cancer·Wayne D Newhauser, Marco Durante
Oct 4, 2011·The Journal of Clinical Investigation·Nicholas R Bertos, Morag Park
Dec 20, 2011·Nature Cell Biology·A BroniszM C Ostrowski

❮ Previous
Next ❯

Citations

Aug 21, 2019·Cold Spring Harbor Perspectives in Medicine·Katie A ThiesMichael C Ostrowski
Jun 26, 2020·Frontiers in Nutrition·Ajit Venniyoor
Sep 26, 2020·Journal of Internal Medicine·B M Lichtenberger, M Kasper
May 7, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carina StrellArne Östman
Jun 14, 2021·Breast Cancer Research : BCR·Katie A ThiesSteven T Sizemore
Jul 13, 2021·JCO Precision Oncology·Andrea M PeschCorey W Speers

❮ Previous
Next ❯

Datasets Mentioned

BETA
GMS
GSE93784

Methods Mentioned

BETA
chromosomal aberrations
X-ray
enzyme-linked immunosorbent assays
biopsy
electrophoresis
Assay
PCR
FACS
enzyme-linked
ELISAs

Software Mentioned

ZEN
Adobe Photoshop
VECTRA
Inform
FlowJo
Degradometer
ImageJ
GSEA
Image
Image J

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.