TY - JOUR
T1 - A novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance
AU - Elsarraj, Hanan S.
AU - Hong, Yan
AU - Valdez, Kelli
AU - Carletti, Martha
AU - Salah, Sally M.
AU - Raimo, Monica
AU - Taverna, Daniela
AU - Prochasson, Philippe
AU - Bharadwaj, Uddalak
AU - Tweardy, David J.
AU - Christenson, Lane K.
AU - Behbod, Fariba
PY - 2013/6
Y1 - 2013/6
N2 - In this report, we have shown that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice than in virgin mice. Furthermore, miR146b levels were significantly higher in mouse mammary glands exposed to the sex hormones, estrogen and progesterone, compared with those of untreated control animals. Pregnancy-derived primary mouse mammary epithelial cells in which miR146b was knocked down showed a significant reduction in the number of hollow acinar organoid structures formed on three-dimensional Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures, whereas solid organoid structures are derived from stem cells. Among several miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cell death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that during pregnancy miR146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating STAT3β
AB - In this report, we have shown that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice than in virgin mice. Furthermore, miR146b levels were significantly higher in mouse mammary glands exposed to the sex hormones, estrogen and progesterone, compared with those of untreated control animals. Pregnancy-derived primary mouse mammary epithelial cells in which miR146b was knocked down showed a significant reduction in the number of hollow acinar organoid structures formed on three-dimensional Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy-derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures, whereas solid organoid structures are derived from stem cells. Among several miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cell death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that during pregnancy miR146b is involved in luminal alveolar progenitor cell maintenance, at least partially, by regulating STAT3β
KW - Alveolar Progenitors
KW - MicroRNA-146b
KW - STAT3
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U2 - 10.1242/jcs.119214
DO - 10.1242/jcs.119214
M3 - Article
C2 - 23572509
AN - SCOPUS:84879999275
SN - 0021-9533
VL - 126
SP - 2446
EP - 2458
JO - Journal of cell science
JF - Journal of cell science
IS - 11
ER -