Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis.
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.
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Dong-Hui
DH
Shin
Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Republic of Korea.
Ji-Hye
JH
Park
Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Republic of Korea.
Jeong-Yeon
JY
Lee
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Hee-Young
HY
Won
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Ki-Seok
KS
Jang
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Kyueng-Whan
KW
Min
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.
Si-Hyong
SH
Jang
College of Pharmacy, Gachon University, Incheon, Republic of Korea.
Jong-Kyu
JK
Woo
College of Pharmacy, Gachon University, Incheon, Republic of Korea.
Seung Hyun
SH
Oh
Department of Pathology, College of Medicine, Hanyang University, Seoul, Republic of Korea.|Institute for Bioengineering and Biopharmaceutical Research (IBBR), Hanyang University, Seoul, Republic of Korea.
Gu
G
Kong
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D005260:Female; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009857:Oncogenes / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1
Id1; basal-like breast cancer; c-Myc; cancer stem cell; mammary stem cell