Abstract
Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 715-729 |
| Number of pages | 15 |
| Journal | Cell Reports |
| Volume | 1 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 28 2012 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
FoxM1 Regulates Mammary Luminal Cell Fate. / Carr, Janai R.; Kiefer, Megan M.; Park, Hyun Jung; Li, Jing; Wang, Zebin; Fontanarosa, Joel; DeWaal, Danielle; Kopanja, Dragana; Benevolenskaya, Elizaveta V.; Guzman, Grace; Raychaudhuri, Pradip.
In: Cell Reports, Vol. 1, No. 6, 28.06.2012, p. 715-729.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - FoxM1 Regulates Mammary Luminal Cell Fate
AU - Carr, Janai R.
AU - Kiefer, Megan M.
AU - Park, Hyun Jung
AU - Li, Jing
AU - Wang, Zebin
AU - Fontanarosa, Joel
AU - DeWaal, Danielle
AU - Kopanja, Dragana
AU - Benevolenskaya, Elizaveta V.
AU - Guzman, Grace
AU - Raychaudhuri, Pradip
PY - 2012/6/28
Y1 - 2012/6/28
N2 - Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.
AB - Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.
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UR - http://www.scopus.com/inward/citedby.url?scp=84863107923&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2012.05.005
DO - 10.1016/j.celrep.2012.05.005
M3 - Article
C2 - 22813746
AN - SCOPUS:84863107923
VL - 1
SP - 715
EP - 729
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 6
ER -