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BET-directed PROTACs in triple negative breast cancer cell lines MDA-MB-231 and MDA-MB-436.
Teufelsbauer, Maryana; Stickler, Sandra; Eggerstorfer, Marie-Therese; Hammond, Dennis Clyde; Hamilton, Gerhard.
Afiliación
  • Teufelsbauer M; Clinics of Plastic and Reconstructive Surgery, Medical University of Vienna, Vienna, Austria.
  • Stickler S; Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
  • Eggerstorfer MT; Institute of Pharmacology, Medical University of Vienna, Vienna, Austria.
  • Hammond DC; Center for Breast and Body Contouring, Grand Rapids, MI, 49546, USA.
  • Hamilton G; Institute of Pharmacology, Medical University of Vienna, Vienna, Austria. gerhard.hamilton@meduniwien.ac.at.
Breast Cancer Res Treat ; 208(1): 89-101, 2024 Nov.
Article en En | MEDLINE | ID: mdl-38896334
ABSTRACT

PURPOSE:

This study aims to find whether the proliferation and migration of triple negative breast cancer (TNBC) cell lines can be reduced by treatment with bromodomain and extra-terminal domain (BET) inhibitor JQ1 and BET protein targeting chimeras (PROTACs) ARV-771 and MZ1.

METHODS:

Cytotoxicity tests, scratch migration assays and western blot proteome profiler arrays for protein expression of cancer-related proteins were used to evaluate the impact of a BET-inhibitor and two BET-directed PROTACs on cell viability, migration and on protein expression.

RESULTS:

JQ1 and the PROTACs MZ1 and ARV-771 significantly inhibited the growth and migration of the KRAS G13D-mutated MDA-MB-231 cells. In this cell line, the PROTACs suppressed the residual expression of ERBB2/HER2, 3 and 4 that are essential for the proliferation of breast cancer cells and this cell line proved sensitive to HER2 inhibitors. In contrast, the effects of the PROTACs on the protein expression of MDA-MB-436 cells mostly affected cytokines and their cognate receptors.

CONCLUSION:

The degradation of BET-protein by PROTACs demonstrated significant anti-proliferative effects. The KRAS-mutated MDA-MB-231 cells belong to the low-HER2 expressing tumors that have a poorer prognosis compared to HER2-null patients. Since first oral PROTACs against tumor hormone receptors are in clinical trials, this mode of tumor therapy is expected to become an important therapeutic strategy in the future treatment of TNBC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Proliferación Celular / Neoplasias de la Mama Triple Negativas Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Movimiento Celular / Proliferación Celular / Neoplasias de la Mama Triple Negativas Límite: Female / Humans Idioma: En Revista: Breast Cancer Res Treat Año: 2024 Tipo del documento: Article País de afiliación: Austria Pais de publicación: Países Bajos