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pH and the Breast Cancer Recurrent Mutation D538G Affect the Process of Activation of Estrogen Receptor α.
de Oliveira, Vinícius M; Dias, Marieli M G; Avelino, Thayná M; Videira, Natália B; da Silva, Fernando B; Doratioto, Tábata R; Whitford, Paul C; Leite, Vitor B P; Figueira, Ana Carolina M.
Afiliación
  • de Oliveira VM; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
  • Dias MMG; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
  • Avelino TM; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
  • Videira NB; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
  • da Silva FB; Department of Physics, São Paulo State University (UNESP), Institute of Biosciences, Humanities and Exact Sciences, São José do Rio Preto 01140-070, SP, Brazil.
  • Doratioto TR; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
  • Whitford PC; Department of Physics, Northeastern University, Boston, Massachusetts 02115, United States.
  • Leite VBP; Department of Physics, São Paulo State University (UNESP), Institute of Biosciences, Humanities and Exact Sciences, São José do Rio Preto 01140-070, SP, Brazil.
  • Figueira ACM; Brazilian Biosciences National Laboratory, National Center for Research in Energy and Materials, LNBio/CNPEM, Campinas 13083-970, SP, Brazil.
Biochemistry ; 61(6): 455-463, 2022 03 15.
Article en En | MEDLINE | ID: mdl-35238537
Estrogen receptor α (ERα) is a regulatory protein that can access a set of distinct structural configurations. ERα undergoes extensive remodeling as it interacts with different agonists and antagonists, as well as transcription activation and repression factors. Moreover, breast cancer tumors resistant to hormone therapy have been associated with the imbalance between the active and inactive ERα states. Cancer-activating mutations in ERα play a crucial role in this imbalance and can promote the progression of cancer. However, the rate of this progression can also be increased by dysregulated pH in the tumor microenvironment. Many molecular aspects of the process of activation of ERα that can be affected by these pH changes and mutations are still unclear. Thus, we applied computational and experimental techniques to explore the activation process dynamics of ER for environments with different pHs and in the presence of one of the most recurrent cancer-activating mutations, D538G. Our results indicated that the effect of the pH increase associated with the D538G mutation promoted a robust stabilization of the active state of ER. We were also able to determine the main protein regions that have the most potential to influence the activation process under different pH conditions, which may provide targets of future therapeutics for the treatment of hormone-resistant breast cancer tumors. Finally, the approach used here can be applied for proteins associated with the proliferation of other cancer types, which can also have their function affected by small pH changes.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptor alfa de Estrógeno Límite: Female / Humans Idioma: En Revista: Biochemistry Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Mama / Receptor alfa de Estrógeno Límite: Female / Humans Idioma: En Revista: Biochemistry Año: 2022 Tipo del documento: Article País de afiliación: Brasil Pais de publicación: Estados Unidos