Stromal PTEN determines mammary epithelial response to radiotherapy.

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 Commun

journal_title

Nature communications

authors

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

doi

10.1038/s41467-018-05266-6

subject

Has Abstract

pub_date

2018-07-17 00:00:00

pages

2783

issue

1

issn

2041-1723

pii

10.1038/s41467-018-05266-6

journal_volume

9

pub_type

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