Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier

<p>Abstract</p> <p>Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among <it>BRCA1</it> mutation carriers. However, the exact mechanism by which RT reduces incidence of <...

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Main Authors: Chiang Huai-Chin, Nair Sreejith J, Yeh I-Tien, Santillan Alfredo A, Hu Yanfen, Elledge Richard, Li Rong
Format: Article
Language:English
Published: BMC 2012-10-01
Series:Experimental Hematology & Oncology
Subjects:
Online Access:http://www.ehoonline.org/content/1/1/31
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author Chiang Huai-Chin
Nair Sreejith J
Yeh I-Tien
Santillan Alfredo A
Hu Yanfen
Elledge Richard
Li Rong
author_facet Chiang Huai-Chin
Nair Sreejith J
Yeh I-Tien
Santillan Alfredo A
Hu Yanfen
Elledge Richard
Li Rong
author_sort Chiang Huai-Chin
collection DOAJ
description <p>Abstract</p> <p>Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among <it>BRCA1</it> mutation carriers. However, the exact mechanism by which RT reduces incidence of <it>BRCA1</it>-associated cancer remains unclear. Here we studied fresh breast tissue from a <it>BRCA1</it> mutation carrier who was initially treated with a lumpectomy and RT for a unilateral cancer and two years later chose a prophylactic bilateral mastectomy while remaining cancer-free. Flow cytometry analysis demonstrated a strikingly lower luminal cell population in the irradiated breast as compared to the non-irradiated breast, which was confirmed by immunohistochemistry. Furthermore, the irradiated breast tissue exhibited very low progenitor cell activity <it>in vitro</it>. Given the emerging evidence that <it>BRCA1</it> tumors originate from luminal progenitor cells, our observations suggest that preferential and long-lasting elimination of luminal ductal epithelium may partly underlie the mechanism of RT-associated reduction in recurrence of <it>BRCA1</it>-associated cancer.</p>
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spelling doaj.art-d4985f46de074367843fb9c3013ddb372022-12-22T01:22:14ZengBMCExperimental Hematology & Oncology2162-36192012-10-01113110.1186/2162-3619-1-31Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrierChiang Huai-ChinNair Sreejith JYeh I-TienSantillan Alfredo AHu YanfenElledge RichardLi Rong<p>Abstract</p> <p>Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among <it>BRCA1</it> mutation carriers. However, the exact mechanism by which RT reduces incidence of <it>BRCA1</it>-associated cancer remains unclear. Here we studied fresh breast tissue from a <it>BRCA1</it> mutation carrier who was initially treated with a lumpectomy and RT for a unilateral cancer and two years later chose a prophylactic bilateral mastectomy while remaining cancer-free. Flow cytometry analysis demonstrated a strikingly lower luminal cell population in the irradiated breast as compared to the non-irradiated breast, which was confirmed by immunohistochemistry. Furthermore, the irradiated breast tissue exhibited very low progenitor cell activity <it>in vitro</it>. Given the emerging evidence that <it>BRCA1</it> tumors originate from luminal progenitor cells, our observations suggest that preferential and long-lasting elimination of luminal ductal epithelium may partly underlie the mechanism of RT-associated reduction in recurrence of <it>BRCA1</it>-associated cancer.</p>http://www.ehoonline.org/content/1/1/31RadiationLuminal progenitor cellsCell of originBRCA1
spellingShingle Chiang Huai-Chin
Nair Sreejith J
Yeh I-Tien
Santillan Alfredo A
Hu Yanfen
Elledge Richard
Li Rong
Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
Experimental Hematology & Oncology
Radiation
Luminal progenitor cells
Cell of origin
BRCA1
title Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
title_full Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
title_fullStr Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
title_full_unstemmed Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
title_short Association of radiotherapy with preferential depletion of luminal epithelial cells in a <it>BRCA1</it> mutation carrier
title_sort association of radiotherapy with preferential depletion of luminal epithelial cells in a it brca1 it mutation carrier
topic Radiation
Luminal progenitor cells
Cell of origin
BRCA1
url http://www.ehoonline.org/content/1/1/31
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