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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 nor...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627307/
https://www.ncbi.nlm.nih.gov/pubmed/25938540
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author 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
author_facet 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
author_sort Shin, Dong-Hui
collection PubMed
description 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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spelling pubmed-46273072015-12-02 Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis 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 Oncotarget Research Paper 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. Impact Journals LLC 2015-04-16 /pmc/articles/PMC4627307/ /pubmed/25938540 Text en Copyright: © 2015 Shin et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
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
Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title_full Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title_fullStr Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title_full_unstemmed Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title_short Overexpression of Id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
title_sort overexpression of id1 in transgenic mice promotes mammary basal stem cell activity and breast tumorigenesis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4627307/
https://www.ncbi.nlm.nih.gov/pubmed/25938540
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