association of radiotherapy with preferential depletion of luminal epithelial cells in a brca1 mutation carrier放射治疗协会与优惠损耗腔的上皮细胞的brca1突变载体.pdfVIP

Chiang et al. Experimental Hematology Oncology 2012, 1:31 /content/1/1/31 Experimental Hematology Oncology CASE REPORT Open Access Association of radiotherapy with preferential depletion of luminal epithelial cells in a BRCA1 mutation carrier 1 1 2 2 1 2 1* Huai-Chin Chiang , Sreejith J Nair , I-Tien Yeh , Alfredo A Santillan , Yanfen Hu , Richard Elledge and Rong Li Abstract Radiation therapy (RT) after breast conservation therapy has recently been linked with significant reduction in risk of ipsilateral breast cancer among BRCA1 mutation carriers. However, the exact mechanism by which RT reduces incidence of BRCA1-associated cancer remains unclear. Here we studied fresh breast tissue from a BRCA1 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 in vitro. Given the emerging evidence that BRCA1 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 BRCA1-associated cancer. Keywords: Radiation, Luminal progenitor cells, Cell of ori