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.
추출된 의학 개체 (NER)
| 유형 | 영어 표현 | 한국어 / 풀이 | UMLS CUI | 출처 | 등장 |
|---|---|---|---|---|---|
| 해부 | breast
|
유방 | dict | 4 | |
| 해부 | mammary
|
유방 | dict | 3 | |
| 시술 | reduction mammoplasty
|
유방성형술 | dict | 1 | |
| 해부 | epithelium
|
scispacy | 1 | ||
| 해부 | cellular
|
scispacy | 1 | ||
| 해부 | mammary epithelial
|
scispacy | 1 | ||
| 해부 | stroma
|
scispacy | 1 | ||
| 해부 | mammary glands
|
scispacy | 1 | ||
| 합병증 | whole-body
|
scispacy | 1 | ||
| 질환 | breast samples
|
scispacy | 1 | ||
| 질환 | breast cancer patients
|
scispacy | 1 | ||
| 질환 | cancer
|
C0006826
Malignant Neoplasms
|
scispacy | 1 | |
| 질환 | non-tumor
|
scispacy | 1 | ||
| 질환 | breast cancer
|
C0006142
Malignant neoplasm of breast
|
scispacy | 1 | |
| 질환 | Stromal PTEN
|
scispacy | 1 | ||
| 기타 | mice
|
scispacy | 1 | ||
| 기타 | stromal-specific phosphatase
|
scispacy | 1 | ||
| 기타 | Pten
→ phosphatase and tensin homolog
|
scispacy | 1 | ||
| 기타 | epidermal growth factor receptor
|
scispacy | 1 | ||
| 기타 | EGFR
→ epidermal growth factor receptor
|
scispacy | 1 | ||
| 기타 | human tissue
|
scispacy | 1 | ||
| 기타 | patients
|
scispacy | 1 |
MeSH Terms
Animals; Antineoplastic 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
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