Oncotarget

Research Papers:

Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis

Dong-Hui Shin _, Ji-Hye Park, Jeong-Yeon Lee, Hee-Young Won, Ki-Seok Jang, Kyueng-Whan Min, Si-Hyong Jang, Jong-Kyu Woo, Seung Hyun Oh and Gu Kong

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Oncotarget. 2015; 6:17276-17290. https://doi.org/10.18632/oncotarget.3640

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Abstract

Dong-Hui Shin1,*, Ji-Hye Park2,*, Jeong-Yeon Lee2,*, Hee-Young Won1, Ki-Seok Jang1, Kyueng-Whan Min1, Si-Hyong Jang1, Jong-Kyu Woo3, Seung Hyun Oh3, Gu Kong1,2

1Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea

2Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Republic of Korea

3College of Pharmacy, Gachon University, Incheon, Republic of Korea

*These authors have contributed equally to this work

Correspondence to:

Gu Kong, e-mail: gkong@hanyang.ac.kr

Keywords: basal-like breast cancer, cancer stem cell, Id1, mammary stem cell, c-Myc

Received: January 14, 2015     Accepted: April 06, 2015     Published: April 16, 2015

ABSTRACT

Inhibitor of differentiation/DNA binding (Id)1 is a crucial regulator of mammary development and breast cancer progression. However, its effect on stemness and tumorigenesis in mammary epithelial cells remains undefined. Herein, we demonstrate that Id1 induces mammary tumorigenesis by increasing normal and malignant mammary stem cell (MaSC) activities in transgenic mice. MaSC-enriched basal cell expansion and increased self-renewal and in vivo regenerative capacity of MaSCs are observed in the mammary glands of MMTV-Id1 transgenic mice. Furthermore, MMTV-Id1 mice develop ductal hyperplasia and mammary tumors with highly expressed basal markers. Id1 also increases breast cancer stem cell (CSC) population and activity in human breast cancer lines. Moreover, the effects of Id1 on normal and malignant stem cell activities are mediated by the Wnt/c-Myc pathway. Collectively, these findings provide in vivo genetic evidence of Id1 functions as an oncogene in breast cancer and indicate that Id1 regulates mammary basal stem cells by activating the Wnt/c-Myc pathway, thereby contributing to breast tumor development.


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