کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5522734 1546034 2017 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cellular transformation of human mammary epithelial cells by SATB2
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
Cellular transformation of human mammary epithelial cells by SATB2
چکیده انگلیسی


- SATB2 regulates pluripotency and self-renewal.
- SATB2-overexpressing cells gain the properties of progenitor-like cells or cancer stem cells.
- SATB2 regulates the expression of pluripotency maintaining factors Oct-4, Nanog, and c-Myc, and stem cell marker CD44.
- Inhibition of SATB2 in breast cancer stem cells suppresses pluripotency, self-renewal and EMT.

Breast tumors are heterogeneous and carry a small population of progenitor cells that can produce various subtypes of breast cancer. SATB2 (special AT-rich binding protein-2) is a newly identified transcription factor and epigenetic regulator. It is highly expressed in embryonic stem cells, but not in adult tissues, and regulates pluripotency-maintaining factors. However, the molecular mechanisms by which SATB2 induces transformation of human mammary epithelial cells (HMECs) leading to malignant phenotype are unknown. The main goal of this paper is to examine the molecular mechanisms by which SATB2 induces cellular transformation of HMECs into cells that are capable of self-renewal. SATB2-transformed HMECs gain the phenotype of breast progenitor cells by expressing markers of stem cells, pluripotency-maintaining factor, and epithelial to mesenchymal transition. SATB2 is highly expressed in human breast cancer cell lines, primary mammary tissues and cancer stem cells (CSCs), but not in HMECs and normal breast tissues. Chromatin Immunoprecipitation assays demonstrate that SATB2 can directly bind to promoters of Bcl-2, c-Myc, Nanog, Klf4, and XIAP, suggesting a role of SATB2 in regulation of pluripotency, cell survival and proliferation. Furthermore, inhibition of SATB2 by shRNA in breast cancer cell lines and CSCs attenuates cell proliferation and EMT phenotype. Our results suggest that SATB2 induces dedifferentiation/transformation of mature HMECs into progenitor-like cells.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Stem Cell Research - Volume 19, March 2017, Pages 139-147
نویسندگان
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