Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression |
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| Authors: | F Chen A Li S Gao D Hollern M Williams F Liu E A VanSickle E Andrechek C Zhang C Yang R Luo H Xiao |
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| Institution: | 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;4.Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA;5.Cell and Molecular Biology Program, Michigan State University, East Lansing, MI, USA |
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| 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. |
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| Keywords: | TIP30 Mammary progenitor breast cancer ERα FoxA1 |
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