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Increased FNDC5/IRISIN protein expression in breast cancer tissue is associated with obesity in postmenopausal women
  1. María Elena Tejeda1,2,
  2. Patricia Canto1,2,
  3. Alberto Tenorio-Torres3,
  4. Letica Orozco-Arguelles1,2,
  5. Ramón Mauricio Coral-Vázquez4,5,
  6. Alejandro Zentella-Dehesa6,7,
  7. Marcela Leal-García1,2,
  8. Claudia Cecilia Vega-García8,
  9. Verónica Bautista-Piña3,
  10. Juan Pablo Méndez1,2
  1. 1Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, México
  2. 2Subdirección de Investigación Clínica, Dirección de Investigación, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Ciudad de México, México
  3. 3Instituto de Enfermedades de la Mama, FUCAM, Ciudad de México, México
  4. 4Sección de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México, México
  5. 5Subdirección de Enseñanza e Investigación, Centro Médico Nacional “20 de Noviembre”, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, Ciudad de México, México
  6. 6Unidad de Bioquímica, Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán", Ciudad de México, México
  7. 7Departamento de Medicina Genómica y Toxicología Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Ciudad de México, México
  8. 8Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”, Ciudad de México, México
  1. Correspondence to Dr Patricia Canto, Unidad de Investigación en Obesidad, Universidad Nacional Autónoma de México, Ciudad de México, 1400, Mexico; ipcanto{at}yahoo.com.mx; Dr Juan Pablo Méndez, Unidad de Investigación en Obesidad, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, 14000, México; jpmb57{at}yahoo.com

Abstract

Aim To analyse the fibronectin type III domain containing 5 (FNDC5)/irisin expression in tumour tissue of postmenopausal women presenting breast cancer and different body mass indexes (BMIs), proposing that obesity deregulates the expression of FNDC5/irisin at the breast tumour level. In addition, we investigated if different breast cancer cell lines are capable to synthesise this protein.

Methods A total of 150 postmenopausal women (50 with a normal BMI, 50 presenting overweight and 50 having obesity) diagnosed with operable breast cancer were included. FNDC5/irisin expression was determined by immunohistochemistry or by immunocytochemistry. Qualitative analysis of protein expression was performed by the H-Score method, through ImageJ’s IHC Profiler software. Statistical analyses were carried out using STATA V.14.0 (Texas, USA); p value<0.05 was accepted as statistically significant. Statistical power of the study was >80% with a p<0.05.

Results FNDC5/irisin expression in breast cancer tissue of postmenopausal women with obesity was significantly increased when compared with FNDC5/irisin expression in women with a normal BMI (p=0.001). Furthermore, three breast cancer cell lines studied were capable to synthesise and express FNDC5/irisin, being the BT-474 cell line the one that exhibited the highest intensity of expression.

Conclusions Our results confirm that women with breast cancer and obesity exhibit an increased irisin expression in their tumorous tissue compared with women with breast cancer and normal BMI. Likewise, in vitro breast cancer cell lines have the capacity to synthesise and express FNDC5/irisin, without any extracellular stimuli, however the microenvironment surrounding these cells in vivo participates in its regulation.

  • biomarkers
  • tumor
  • breast neoplasms
  • cytokines

Data availability statement

All data relevant to the study are included in the article.

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Data availability statement

All data relevant to the study are included in the article.

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Footnotes

  • Handling editor Cheok Soon Lee.

  • Collaborators José Luis Ventura Gallegos, M.Sc., Brenda Marquina Castillo, M.D., Technicians Gabriela Chávez López and Ricardo Aguilar Guadarrama, Carlos Domínguez Reyes, M.D., and Felipe Villegas Carlos, M.D.

  • Contributors MET: Performed all the experiments, analysis of results and final approval of the version to be published. PC: Design of all experiments and studies, interpretation of the results, manuscript elaboration and final approval of the version to be published. AT-T: Design, inclusion of patients and clinical studies and final approval of the version to be published. LO-A: Performed all the experiments, analysis of results and final approval of the version to be published. RMC-V: Design of all experiments and studies, manuscript elaboration and final approval of the version to be published. AZ-D: Analysis of the breast cancer cell lines. ML-G: Inclusion of patients and clinical studies and final approval of the version to be published. CCV-G: Design, performed the experiments and final approval of the version to be published. VB-P: Design, pathology analysis and final approval of the version to be published. JPM: Grant obtention, design of all experiments and studies, interpretation of the results and manuscript elaboration.

  • Funding This work was supported by a grant from the División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, México, and by the Consejo Nacional De Ciencia y Tecnología, México: Apoyo al Fortalecimiento y Desarrollo de la Infraestructura Científica y Tecnológica (Grant: 250786).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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