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Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer.
Kimbung, Siker; Chang, Ching-Yi; Bendahl, Pär-Ola; Dubois, Laura; Thompson, J Will; McDonnell, Donald P; Borgquist, Signe.
Afiliação
  • Kimbung S; Division of Oncology and PathologyDepartment of Clinical Sciences, Lund, Lund University, Sweden siker.kimbung@med.lu.se signe.borgquist@med.lu.se.
  • Chang CY; Department of Pharmacology and Cancer BiologyDuke University School of Medicine, Durham, NC, USA.
  • Bendahl PO; Division of Oncology and PathologyDepartment of Clinical Sciences, Lund, Lund University, Sweden.
  • Dubois L; Duke Proteomics and Metabolomics ResourceDuke University School of Medicine, Durham, NC, USA.
  • Thompson JW; Department of Pharmacology and Cancer BiologyDuke University School of Medicine, Durham, NC, USA.
  • McDonnell DP; Duke Proteomics and Metabolomics ResourceDuke University School of Medicine, Durham, NC, USA.
  • Borgquist S; Department of Pharmacology and Cancer BiologyDuke University School of Medicine, Durham, NC, USA.
Endocr Relat Cancer ; 24(7): 339-349, 2017 07.
Article em En | MEDLINE | ID: mdl-28442559
The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical trial. Further, the associations between CYP27A1 expression with other primary tumor pathological features and clinical outcomes were studied in two additional independent cohorts. Statin treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in tumors. However, these changes were not associated with anti-proliferative responses to statin treatment. CYP27A1 was heterogeneously expressed among primary tumors, with high expression significantly associated with high tumor grade, ER negativity and basal-like subtype. High CYP27A1 expression was independently prognostic for longer recurrence-free and overall survival. Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer seemed limited to women aged ≤50 years. These results establish a link between CYP27A1 and breast cancer pathobiology and prognosis and propose that the efficacy of statins in reducing serum lipids does not directly translate to anti-proliferative effects in tumors. Changes in other undetermined serum or tumor factors suggestively mediate the anti-proliferative effects of statins in breast cancer.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Inibidores de Hidroximetilglutaril-CoA Redutases / Colestanotriol 26-Mono-Oxigenase / Hidroxicolesteróis Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged Idioma: En Revista: Endocr Relat Cancer Assunto da revista: ENDOCRINOLOGIA / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Inibidores de Hidroximetilglutaril-CoA Redutases / Colestanotriol 26-Mono-Oxigenase / Hidroxicolesteróis Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Middle aged Idioma: En Revista: Endocr Relat Cancer Assunto da revista: ENDOCRINOLOGIA / NEOPLASIAS Ano de publicação: 2017 Tipo de documento: Article