Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
Date
2022-06-06ICR Author
Author
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
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Animals
Breast Neoplasms
Estradiol
Female
Humans
Mice
Progesterone
Receptors, Estrogen
Receptors, Progesterone
Research team
Endocrine control mechans
Language
eng
Date accepted
2022-05-24
License start date
2022-06-06
Citation
Nature Communications, 2022, 13 (1), pp. 3127 -
Publisher
NATURE PORTFOLIO