Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
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Embargo End Date
ICR Authors
Authors
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
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
Document Type
Journal Article
Date
2022-06-06
Date Accepted
2022-05-24
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.
Citation
Nature Communications, 2022, 13 (1), pp. 3127 -
Source Title
Nature Communications
Publisher
NATURE PORTFOLIO
ISSN
2041-1723
eISSN
2041-1723
2041-1723
2041-1723
Collections
Research Team
Endocrine control mechans