Cargando…
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...
Autores principales: | , , , , , , , , , |
---|---|
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 |
_version_ | 1782398268225880064 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4627307 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT shindonghui overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT parkjihye overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT leejeongyeon overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT wonheeyoung overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT jangkiseok overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT minkyuengwhan overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT jangsihyong overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT woojongkyu overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT ohseunghyun overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis AT konggu overexpressionofid1intransgenicmicepromotesmammarybasalstemcellactivityandbreasttumorigenesis |