Estrogen receptor positive breast cancers have patient specific hormone sensitivities and rely on progesterone receptor.
Nat Commun
; 13(1): 3127, 2022 06 06.
Article
em En
| MEDLINE
| ID: mdl-35668111
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-ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Receptores de Progesterona
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Nat Commun
Ano de publicação:
2022
Tipo de documento:
Article