Establishment of a normal-derived estrogen receptor-positive cell line comparable to the prevailing human breast cancer subtype
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Branden M. Hopkinson1,2, Marie C. Klitgaard1,2,3, Ole William Petersen1,2, René Villadsen1,2, Lone Rønnov-Jessen3, Jiyoung Kim1,2
1Department of Cellular and Molecular Medicine, University of Copenhagen, DK-2200 Copenhagen, Denmark
2Danish Stem Cell Centre, University of Copenhagen, DK-2200 Copenhagen, Denmark
3Department of Biology, University of Copenhagen, DK-2100 Copenhagen, Denmark
Jiyoung Kim, email: [email protected]
Lone Rønnov-Jessen, email: [email protected]
Keywords: human breast, breast cancer, estrogen receptor, immortalized luminal cells
Received: July 10, 2016 Accepted: December 12, 2016 Published: January 06, 2017
Understanding human cancer increasingly relies on insight gained from subtype specific comparisons between malignant and non-malignant cells. The most frequent subtype in breast cancer is the luminal. By far the most frequently used model for luminal breast cancer is the iconic estrogen receptor-positive (ERpos) MCF7 cell line. However, luminal specific comparisons have suffered from the lack of a relevant non-malignant counterpart. Our previous work has shown that transforming growth factor-β receptor (TGFβR) inhibition suffices to propagate prospectively isolated ERpos human breast luminal cells from reduction mammoplasties (HBEC). Here we demonstrate that transduction of these cells with hTERT/shp16 renders them immortal while remaining true to the luminal lineage including expression of functional ER (iHBECERpos). Under identical culture conditions a major difference between MCF7 and normal-derived cells is the dependence of the latter on TGFβR inhibition for ER expression. In a breast fibroblast co-culture model we further show that whereas MCF7 proliferate concurrently with ER expression, iHBECERpos form correctly polarized acini, and segregate into proliferating and ER expressing cells. We propose that iHBECERpos may serve to shed light on hitherto unappreciated differences in ER regulation and function between normal breast and breast cancer.
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