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GEO help: Mouse over screen elements for information. |
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Status |
Public on Jun 13, 2018 |
Title |
Stromal PTEN determines mammary epithelial response to radio-therapy |
Organism |
Mus musculus |
Experiment type |
Expression profiling by array
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Summary |
It is well-described that the tumor stroma participates in cancer progression, but whether stromal factors can initiate breast tumorigenesis remains unclear. Using our previously described stromal-specific phosphatase and tensin homolog (PTEN) deletion mouse model, we investigated transformative events in young, non-tumor bearing animals. Here, we show stromal PTEN deletion initiates radiation-induced genomic instability on neighboring mammary epithelium through paracrine epidermal growth factor receptor (EGFR) activation. In these mice, a single low dose of whole-body radiation induces mammary hyperplasia, a result that is prevented by pre-treatment with an EGFR inhibitor. We reveal that stromal PTEN is lost in a subset of normal breast samples and is predictive of recurrence in breast cancer patients. Combined, these data suggest both diagnostic and therapeutic chest wall radiotherapy may inadvertently predispose patients with focal stromal PTEN loss to secondary breast cancer, and that this predisposition may be treated prophylactically through EGFR inhibition.
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Overall design |
Each biological replicate of FACS sorted Lin-CD24+CD29loCD61- mature luminal epithelial subpopulations was collected by pooling pre-neoplastic mammary tissue from 6-8 virgin ErbB2;Ptenfl/fl or ErbB2;Fsp-cre;Ptenfl/fl (8-9 weeks of age) mice. Microarray on three mature luminal samples from both genetic groups was performed with GeneChip® Mouse Transcriptome Assay 1.0 (Affymetrix, Santa Clara, California, USA) at the OSUCCC Genomics Facility.
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Contributor(s) |
Sizemore GM, Balakrishnan S, Ostrowski MC |
Citation(s) |
30018330 |
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Submission date |
Jan 18, 2017 |
Last update date |
May 21, 2019 |
Contact name |
Gina Sizemore |
E-mail(s) |
gmb15@case.edu
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Phone |
614-685-9185
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Organization name |
Ohio State University
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Street address |
460 W. 12th Avenue
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City |
Columbus |
State/province |
OH |
ZIP/Postal code |
43210 |
Country |
USA |
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Platforms (1) |
GPL20775 |
[MTA-1_0] Affymetrix Mouse Transcriptome Array 1.0 [transcript (gene) CSV version] |
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Samples (6)
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GSM2462076 |
Mature Luminal population isolated from control ErbB2 mice-Experiment#1 |
GSM2462077 |
Mature Luminal population isolated from control ErbB2 mice-Experiment#2 |
GSM2462078 |
Mature Luminal population isolated from control ErbB2 mice-Experiment#3 |
GSM2462079 |
Mature Luminal population isolated from ErbB2, stromal PTEN deletion mice-Experiment#1 |
GSM2462080 |
Mature Luminal population isolated from ErbB2, stromal PTEN deletion mice-Experiment#2 |
GSM2462081 |
Mature Luminal population isolated from ErbB2, stromal PTEN deletion mice-Experiment#3 |
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Relations |
BioProject |
PRJNA362364 |
Supplementary file |
Size |
Download |
File type/resource |
GSE93784_RAW.tar |
130.9 Mb |
(http)(custom) |
TAR (of CEL) |
Processed data included within Sample table |
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