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

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

doi:10.1038/cddis.2014.224

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

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

Markey Cancer Center / Cancer Research Priority Initiative

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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.

Original language	English
Journal	Cell Death and Disease
Volume	5
DOIs	https://doi.org/10.1038/cddis.2014.224
State	Published - 2014

Bibliographical note

Funding Information:
Acknowledgements. We are grateful to Jill Pecha for backcrossing Tip30 knockout gene into Balb/c mice and Ying Qin for histological examination of preneoplastic lesions and tumors. This work was supported by NIDDK grant DK066110-01 and DOD grant W81XWH-08-1-0377 to H Xiao, Komen grant KG110510 and NCI grant 1R01CA160514-01A1 to E Andrechek and Guangdong Natural Science Foundation grant (10151051501000050) to A Li F Chen and A Li were supported in part by fellowships from Nanfang Hospital, China. M Williams was supported by NIH 5T32GM92715 training grant. CY was supported by National Institute of Health (1R01ES017777-01A1).

Funding

Acknowledgements. We are grateful to Jill Pecha for backcrossing Tip30 knockout gene into Balb/c mice and Ying Qin for histological examination of preneoplastic lesions and tumors. This work was supported by NIDDK grant DK066110-01 and DOD grant W81XWH-08-1-0377 to H Xiao, Komen grant KG110510 and NCI grant 1R01CA160514-01A1 to E Andrechek and Guangdong Natural Science Foundation grant (10151051501000050) to A Li F Chen and A Li were supported in part by fellowships from Nanfang Hospital, China. M Williams was supported by NIH 5T32GM92715 training grant. CY was supported by National Institute of Health (1R01ES017777-01A1).

Funders	Funder number
National Institutes of Health (NIH)	5T32GM92715, 1R01ES017777-01A1
U.S. Department of Defense	W81XWH-08-1-0377, KG110510
National Childhood Cancer Registry – National Cancer Institute	R01CA160514
National Institute of Diabetes and Digestive and Kidney Diseases	DK066110-01
Natural Science Foundation of Guangdong Province	10151051501000050

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

ASJC Scopus subject areas

Immunology
Cellular and Molecular Neuroscience
Cell Biology
Cancer Research

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10.1038/cddis.2014.224

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

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.",

author = "F. Chen and A. Li and S. Gao and D. Hollern and M. Williams and F. Liu and VanSickle, \{E. A.\} and E. Andrechek and C. Zhang and C. Yang and R. Luo and H. Xiao",

note = "Funding Information: Acknowledgements. We are grateful to Jill Pecha for backcrossing Tip30 knockout gene into Balb/c mice and Ying Qin for histological examination of preneoplastic lesions and tumors. This work was supported by NIDDK grant DK066110-01 and DOD grant W81XWH-08-1-0377 to H Xiao, Komen grant KG110510 and NCI grant 1R01CA160514-01A1 to E Andrechek and Guangdong Natural Science Foundation grant (10151051501000050) to A Li F Chen and A Li were supported in part by fellowships from Nanfang Hospital, China. M Williams was supported by NIH 5T32GM92715 training grant. CY was supported by National Institute of Health (1R01ES017777-01A1).",

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T1 - Tip30 controls differentiation of murine mammary luminal progenitor to estrogen receptor-positive luminal cell through regulating FoxA1 expression.

AU - Chen, F.

AU - Li, A.

AU - Gao, S.

AU - Hollern, D.

AU - Williams, M.

AU - Liu, F.

AU - VanSickle, E. A.

AU - Andrechek, E.

AU - Zhang, C.

AU - Yang, C.

AU - Luo, R.

AU - Xiao, H.

N1 - Funding Information: Acknowledgements. We are grateful to Jill Pecha for backcrossing Tip30 knockout gene into Balb/c mice and Ying Qin for histological examination of preneoplastic lesions and tumors. This work was supported by NIDDK grant DK066110-01 and DOD grant W81XWH-08-1-0377 to H Xiao, Komen grant KG110510 and NCI grant 1R01CA160514-01A1 to E Andrechek and Guangdong Natural Science Foundation grant (10151051501000050) to A Li F Chen and A Li were supported in part by fellowships from Nanfang Hospital, China. M Williams was supported by NIH 5T32GM92715 training grant. CY was supported by National Institute of Health (1R01ES017777-01A1).

PY - 2014

Y1 - 2014

N2 - 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.

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

Abstract

Bibliographical note

Funding

UN SDGs

ASJC Scopus subject areas

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