Summary of project PR001711
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001711. The data can be accessed directly via it's Project DOI: 10.21228/M8JD9D This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR001711 |
| Project DOI: | doi: 10.21228/M8JD9D |
| Project Title: | HER2 related MMTV-Neu mammary ducts studies |
| Project Type: | MS quantitative analysis |
| Project Summary: | Metabolomics analysis of intact mammary ducts. HER2 is a driver oncogene overexpressed in the majority of premalignant breast tumors known as ductal carcinoma in situ (DCIS). Due to their stemness features, breast cancer stem cells (BCSC) are considered the main drivers of breast tumor initiation and progression. Here, we used clinical samples and mouse models of HER2+ breast tumorigenesis to demonstrate that neither BCSCs nor their cell-of-origin express HER2/Neu in early-stage breast tumors. Instead, our results demonstrate that Neu overexpression results in the transformation of BCSCs in a non-cell autonomous manner via triggering DNA damage and somatic mutagenesis in their Neu-negative cell-of-origin. This is caused by the increased oxidative stress in the tissue microenvironment generated by altered energy metabolism and increased reactive oxygen species level in Neu-overexpressing mammary ducts. Therefore, our findings illustrate a previously unrecognized mechanism of HER2-induced breast tumor initiation, which may have an impact on future preventive treatments for patients with HER2+ DCIS. |
| Institute: | The University of Manchester |
| Department: | Faculty of Biology, Medicine and Health |
| Laboratory: | Ahmet Ucar Lab |
| Last Name: | Ou |
| First Name: | Yaqing |
| Address: | Oxford Road, Manchester, Great Manchester, M13 9PL, United Kingdom |
| Email: | yaqing.ou@manchester.ac.uk |
| Phone: | 07579759914 |
| Contributors: | Sevim B. Gurler, Oliver Wagstaff, Lili Dimitrova, Fuhui Chen, Robert Pedley, William Weston, Ian Donaldson, Brian A. Telfer, David Novo, Kyriaki Pavlou, George Taylor, Yaqing Ou, Kaye J. Williams, Andrew Gilmore, Keith Brennan, Ahmet Ucar |
Summary of all studies in project PR001711
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002748 | HER2 overexpression initiates breast tumorigenesis non-cell autonomously by inducing oxidative stress in the tissue microenvironment | Mus musculus | The University of Manchester | MS* | 2024-07-10 | 1 | 7 | Uploaded data (3.5M)* |
