Title

Stromal PTEN determines mammary epithelial response to radiotherapy

Authors

Gina M. Sizemore, The Ohio State University Comprehensive Cancer Center
Subhasree Balakrishnan, The Ohio State University Comprehensive Cancer Center
Katie A. Thies, Medical University of South Carolina
Anisha M. Hammer, The Ohio State University Comprehensive Cancer Center
Steven T. Sizemore, The Ohio State University Comprehensive Cancer Center
Anthony J. Trimboli, Medical University of South Carolina
Maria C. Cuitiño, Medical University of South Carolina
Sarah A. Steck, The Ohio State University Comprehensive Cancer Center
Gary Tozbikian, The Ohio State University Wexner Medical Center
Raleigh D. Kladney, The Ohio State University Comprehensive Cancer Center
Neelam Shinde, The Ohio State University Comprehensive Cancer Center
Manjusri Das, The Ohio State University Comprehensive Cancer Center
Dongju Park, The Ohio State University Comprehensive Cancer Center
Sarmila Majumder, The Ohio State University Comprehensive Cancer Center
Shiva Krishnan, The Ohio State University Comprehensive Cancer Center
Lianbo Yu, The Ohio State University
Soledad A. Fernandez, The Ohio State University
Arnab Chakravarti, The Ohio State University Comprehensive Cancer Center
Peter G. Shields, The Ohio State University Comprehensive Cancer Center
Julia R. White, The Ohio State University Comprehensive Cancer Center
Lisa D. Yee, City of Hope National Med Center
Thomas J. Rosol, Ohio University
Thomas Ludwig, The Ohio State University Comprehensive Cancer Center
Morag Park, McGill University, Rosalind and Morris Goodman Cancer Research Centre
Gustavo Leone, Medical University of South Carolina
Michael C. Ostrowski, Medical University of South Carolina

Document Type

Article

Publication Date

12-1-2018

Abstract

© 2018 The Author(s). 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.

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