Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.

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State: Public
Version: Final published version
License: CC BY 4.0
Serval ID
serval:BIB_BED35CC8098E
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
Journal
Nature communications
Author(s)
Scabia V., Ayyanan A., De Martino F., Agnoletto A., Battista L., Laszlo C., Treboux A., Zaman K., Stravodimou A., Jallut D., Fiche M., Bucher P., Ambrosini G., Sflomos G., Brisken C.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Publication state
Published
Issued date
06/06/2022
Peer-reviewed
Oui
Volume
13
Number
1
Pages
3127
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Estrogen and progesterone receptor (ER, PR) signaling control breast development and impinge on breast carcinogenesis. ER is an established driver of ER + disease but the role of the PR, itself an ER target gene, is debated. We assess the issue in clinically relevant settings by a genetic approach and inject ER + breast cancer cell lines and patient-derived tumor cells to the milk ducts of immunocompromised mice. Such ER + xenografts were exposed to physiologically relevant levels of 17-β-estradiol (E2) and progesterone (P4). We find that independently both premenopausal E2 and P4 levels increase tumor growth and combined treatment enhances metastatic spread. The proliferative responses are patient-specific with MYC and androgen receptor (AR) signatures determining P4 response. PR is required for tumor growth in patient samples and sufficient to drive tumor growth and metastasis in ER signaling ablated tumor cells. Our findings suggest that endocrine therapy may need to be personalized, and that abrogating PR expression can be a therapeutic option.
Keywords
Animals, Breast Neoplasms/metabolism, Estradiol/pharmacology, Estradiol/therapeutic use, Female, Humans, Mice, Progesterone/pharmacology, Receptors, Estrogen/genetics, Receptors, Estrogen/metabolism, Receptors, Progesterone/genetics, Receptors, Progesterone/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
24/06/2022 17:56
Last modification date
23/01/2024 8:33
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