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Estradiol induces bone osteolysis in triple-negative breast cancer via its membrane-associated receptor ERα36.
Cohen, D Joshua; Dennis, Cydney D; Deng, Jingyao; Boyan, Barbara D; Schwartz, Zvi.
Afiliación
  • Cohen DJ; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, United States.
  • Dennis CD; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, United States.
  • Deng J; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, United States.
  • Boyan BD; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23284, United States.
  • Schwartz Z; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, United States.
JBMR Plus ; 8(5): ziae041, 2024 May.
Article en En | MEDLINE | ID: mdl-38644978
ABSTRACT
Triple-negative breast cancer (TNBC) is thought to be an estradiol-independent, hormone therapy-resistant cancer because of lack of estrogen receptor alpha 66 (ERα66). We identified a membrane-bound splice variant, ERα36, in TNBC cells that responds to estrogen (E2) and may contribute to bone osteolysis. We demonstrated that the MDA-MB-231 TNBC cell line, which expresses ERα36 similarly to MCF7 cells, is responsive to E2, forming osteolytic tumors in vivo. MDA-MB-231 cells activate osteoclasts in a paracrine manner. Conditioned media (CM) from MDA-MB-231 cells treated with bovine serum albumin-bound E2 (E2-BSA) increased activation of human osteoclast precursor cells; this was blocked by addition of anti-ERα36 antibody to the MDA-MB-231 cultures. Osteoclast activation and bone resorption genes were elevated in RAW 264.7 murine macrophages following treatment with E2-BSA-stimulated MDA-MB-231 CM. E2 and E2-BSA increased phospholipase C (PLC) and protein kinase C (PKC) activity in MDA-MB-231 cells. To examine the role of ERα36 signaling in bone osteolysis in TNBC, we used our bone-cancer interface mouse model in female athymic homozygous Foxn1nu mice. Mice with MDA-MB-231 tumors and treated with tamoxifen (TAM), E2, or TAM/E2 exhibited increased osteolysis, cortical bone breakdown, pathologic fracture, and tumor volume; the combined E2/TAM group also had reduced bone volume. These results suggest that E2 increased osteolytic lesions in TNBC through a membrane-mediated PLC/PKC pathway involving ERα36, which was enhanced by TAM, demonstrating the role of ERα36 and its membrane-associated signaling pathway in bone tumors. This work suggests that ERα36 may be a potential therapeutic target in patients with TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JBMR Plus Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: JBMR Plus Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido