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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
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,Yeedoi
10.1038/s41467-018-05266-6subject
Has Abstractpub_date
2018-07-17 00:00:00pages
2783issue
1issn
2041-1723pii
10.1038/s41467-018-05266-6journal_volume
9pub_type
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