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Cell Death Dis. 2014 May 22;5:e1242. doi: 10.1038/cddis.2014.224.

Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression.

Author information

1
1] Department of Physiology, Michigan State University, East Lansing, MI, USA [2] Cancer Center, Southern Medical University, Guangzhou, China [3] Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Southern Medical University, Guangzhou, China.
2
1] Department of Physiology, Michigan State University, East Lansing, MI, USA [2] Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
3
Department of Physiology, Michigan State University, East Lansing, MI, USA.
4
1] Department of Physiology, Michigan State University, East Lansing, MI, USA [2] Cell and Molecular Biology Program, Michigan State University, East Lansing, MI, USA.
5
1] Department of Physiology, Michigan State University, East Lansing, MI, USA [2] Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Southern Medical University, Guangzhou, China.
6
1] Cancer Center, Southern Medical University, Guangzhou, China [2] Traditional Chinese Medicine-Integrated Hospital, Southern Medical University, Southern Medical University, Guangzhou, China.

Abstract

Estrogen receptor-alpha positive (ER(+)) breast cancers comprise the majority of human breast cancers, but molecular mechanisms underlying this subtype of breast cancers remain poorly understood. Here, we show that ER(+) mammary luminal tumors arising in Tip30(-/-)MMTV-Neu mice exhibited increased enrichment of luminal progenitor gene signature. Deletion of the Tip30 gene increased proportion of mammary stem and progenitor cell populations, and raised susceptibility to ER(+) mammary luminal tumors in female Balb/c mice. Moreover, Tip30(-/-) luminal progenitors displayed increases in propensity to differentiate to mature ER(+) luminal cells and FoxA1 expression. Knockdown of FoxA1 expression in Tip30(-/-) progenitors by shRNA specific for FoxA1 reduced their differentiation toward ER(+) mature luminal cells. Taken together, our results suggest that TIP30 is a key regulator for maintaining ER(+) and ER(-)luminal pools in the mammary luminal lineage, and loss of it promotes expansion of ER(+) luminal progenitors and mature cells and ER(+) mammary tumorigenesis.

PMID:
24853420
PMCID:
PMC4047867
DOI:
10.1038/cddis.2014.224
[Indexed for MEDLINE]
Free PMC Article

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