Summary of Study ST002748

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

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002748
Study TitleHER2 overexpression initiates breast tumorigenesis non-cell autonomously by inducing oxidative stress in the tissue microenvironment
Study SummaryHER2 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
DepartmentManchester Breast Centre
LaboratoryAhmet Ucar Lab
Last NameUcar
First NameAhmet
AddressOxford Road, Manchester, M13 9PL, UK.
Emailahmet.ucar@manchester.ac.uk
Phone+44 (0)161 3067116
Submit Date2023-06-26
Raw Data AvailableYes
Raw Data File Type(s)wiff
Analysis Type DetailLC-MS
Release Date2024-07-10
Release Version1
Ahmet Ucar Ahmet Ucar
https://dx.doi.org/10.21228/M8JD9D
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id local_sample_id Genotype Treatment
SA289304407 668Mutant MMTV-NIC
SA289305407 667Mutant MMTV-NIC
SA289306407 663Mutant MMTV-NIC
SA289307407 662Mutant MMTV-NIC
SA289308407 661Wild-type Control
SA289309407 669Wild-type Control
SA289310407 660Wild-type Control
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