PXD067122-1

PXD067122 is an original dataset announced via ProteomeXchange.

Title	BC-APPS1: Anti-progestin therapy targets hallmarks of breast cancer risk through epithelial-stromal remodelling
Description	Breast cancer (BC) is the leading cause of women's cancer death worldwide. Here, in the BC – Anti Progestin Prevention Study 1 (BC-APPS1; NCT02408770), we assess whether progesterone receptor antagonism with ulipristal acetate (UA) for 12 weeks reduces surrogate markers of BC risk in 24 premenopausal women. We employ a multi-layered OMICs and live-cell approach as readouts for molecular features alongside clinical imaging and tissue micro-mechanics correlates. UA reduced epithelial proliferation (Ki67) and the proportion, proliferation, and colony formation capacity of luminal progenitor (LP) cells, the precursors of aggressive BCs. MRI scans showed reduction in fibroglandular volume with treatment, while single-cell RNAseq, proteomics, histology and atomic force microscopy identified extracellular matrix remodelling with reduced collagen organisation and tissue stiffness. Laser capture targeted mass spectrometry revealed Ccollagen VI as the most significantly down-regulated protein after UA treatment and we uncovered an unanticipated spatial association between Collagen VI and Sox9hi LP cell localization, establishing a link between collagen organization and LP activity. This study offers a template for molecularly informed early phase prevention trials and demonstrates the potential for premenopausal BC prevention with progesterone receptor antagonists through stromal remodelling and LP suppression.
HostingRepository	PRIDE
AnnounceDate	2025-09-04
AnnouncementXML	Submission_2025-09-04_00:57:58.989.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Gilmore
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	hydroxylated proline; acetylated residue; monohydroxylated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2025-08-08 05:17:37	ID requested
⏵ 1	2025-09-04 00:57:59	announced

Dataset with its publication pending

submitter keyword: prevention,Breast cancer, laser capture proteomics

Andrew Gilmore
contact affiliation	Manchester Cell Matrix Centre | Division of Cancer Sciences | School of Medical Sciences | Faculty of Biology, Medicine and Health The University of Manchester | Michael Smith Building | Oxford Road | Manchester M13 9PT
contact email	andrew.gilmore@manchester.ac.uk
lab head
Andrew Gilmore
contact affiliation	Wellcome Trust Centre for Cell/Matrix Research Division of Cancer Sciences School of Medical Sciences Faculty of Biology, Medicine and Health The University of Manchester
contact email	andrew.gilmore@manchester.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD067122
     1. Label: PRIDE project
     2. Name: BC-APPS1: Anti-progestin therapy targets hallmarks of breast cancer risk through epithelial-stromal remodelling