Other
12 Authors
- Hollern D,
- Andrechek E,
- Liu F,
- Chen F,
- Yang C,
- Xiao H,
- Williams M,
- Zhang C,
- Li A,
- Gao S,
- VanSickle EA,
- Luo R
First Author | Chen F | Year | 2014 |
Journal | Cell Death Dis | Volume | 5 |
Pages | e1242 | PubMed ID | 24853420 |
Mgi Jnum | J:317292 | Mgi Id | MGI:6851903 |
Doi | 10.1038/cddis.2014.224 | Citation | Chen F, et al. (2014) Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression. Cell Death Dis 5:e1242 |
abstractText | 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. |