Shin Dong-Hui, Park Ji-Hye, Lee Jeong-Yeon, Won Hee-Young, Jang Ki-Seok, Min Kyueng-Whan, Jang Si-Hyong, Woo Jong-Kyu, Oh Seung Hyun, Kong Gu
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.
Oncotarget. 2015 Jul 10;6(19):17276-90. doi: 10.18632/oncotarget.3640.
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.
分化/DNA结合抑制因子（Id）1是乳腺发育和乳腺癌进展的关键调节因子。然而，其对乳腺上皮细胞干性和肿瘤发生的影响仍不明确。在此，我们证明Id1通过增加转基因小鼠正常和恶性乳腺干细胞（MaSC）活性诱导乳腺肿瘤发生。在MMTV-Id1转基因小鼠的乳腺中观察到富含MaSC的基底细胞扩张以及MaSCs自我更新和体内再生能力增强。此外，MMTV-Id1小鼠发生导管增生和具有高表达基底标志物的乳腺肿瘤。Id1还增加人乳腺癌细胞系中乳腺癌干细胞（CSC）群体和活性。此外，Id1对正常和恶性干细胞活性的影响由Wnt/c-Myc途径介导。总的来说，这些发现提供了Id1在乳腺癌中作为癌基因功能的体内遗传学证据，并表明Id1通过激活Wnt/c-Myc途径调节乳腺基底干细胞，从而促进乳腺肿瘤发展。
