Stromal PTEN determines mammary epithelial response to radiotherapy. Nat Commun 2018 Jul 17;9(1):2783
Date
07/19/2018Pubmed ID
30018330Pubmed Central ID
PMC6050339DOI
10.1038/s41467-018-05266-6Scopus ID
2-s2.0-85050372792 (requires institutional sign-in at Scopus site) 18 CitationsAbstract
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.
Author List
Sizemore GM, Balakrishnan S, Thies KA, Hammer AM, Sizemore ST, Trimboli AJ, Cuitiño MC, Steck SA, Tozbikian G, Kladney RD, Shinde N, Das M, Park D, Majumder S, Krishnan S, Yu L, Fernandez SA, Chakravarti A, Shields PG, White JR, Yee LD, Rosol TJ, Ludwig T, Park M, Leone G, Ostrowski MCAuthors
Gustavo Leone PhD Sr Associate Dean, Director, Professor in the Biochemistry department at Medical College of WisconsinAnthony J. Trimboli PhD Assistant Professor in the Biochemistry department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnimalsAntineoplastic Agents
Breast Neoplasms
Cell Proliferation
Cell Transformation, Neoplastic
Epithelial Cells
ErbB Receptors
Female
Gamma Rays
Gene Expression Regulation, Neoplastic
Genomic Instability
Humans
Mammary Glands, Animal
Mammary Glands, Human
Mammary Neoplasms, Experimental
Mice
PTEN Phosphohydrolase
Protein Kinase Inhibitors
Radiation Tolerance
Signal Transduction
Stromal Cells
