A B Crujeiras1,2, B Cabia1,2, M C Carreira1,2, M Amil1,2, J Cueva3, S Andrade1,2, L M Seoane4,2, M Pardo5,2, A Sueiro1, J Baltar6, T Morais7, M P Monteiro7, R Lopez-Lopez3, F F Casanueva1,2. 1. Laboratory of Molecular and Cellular Endocrinology, Instituto de Investigación Sanitaria (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS) and Santiago de Compostela University (USC), Santiago de Compostela, Spain. 2. CIBER Fisiopatología de la Obesidad y la Nutrición (CIBERobn), Madrid, Spain. 3. Division of Medical Oncology, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. 4. Grupo Fisiopatologia Endocrina, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. 5. Grupo Obesidomica, Instituto de Investigacion Sanitaria de Santiago de Compostela (IDIS), Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. 6. Division of General Surgery, Complejo Hospitalario Universitario de Santiago (CHUS/SERGAS), Santiago de Compostela, Spain. 7. Clinical and Experimental Endocrinology, Department of Anatomy, Multidisciplinary Unit for Biomedical Research (UMIB), ICBAS, University of Porto, Porto, Portugal.
Abstract
BACKGROUND/ OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.
BACKGROUND/ OBJECTIVES:Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obesewomen and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS:DIOrats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-Srats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obesewomen compared with normal weight women without evidence of breast cancer. CONCLUSIONS:Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.
Authors: Arturo Roca-Rivada; Omar Al-Massadi; Cecilia Castelao; Lucía L Senín; Jana Alonso; Luisa María Seoane; Tomás García-Caballero; Felipe F Casanueva; María Pardo Journal: J Proteomics Date: 2012-07-16 Impact factor: 4.044
Authors: R Fornari; D Francomano; E A Greco; C Marocco; C Lubrano; F Wannenes; V Papa; V M Bimonte; L M Donini; A Lenzi; A Aversa; S Migliaccio Journal: J Endocrinol Invest Date: 2014-10-29 Impact factor: 4.256
Authors: A B Crujeiras; D Gomez-Arbelaez; M A Zulet; M C Carreira; I Sajoux; D de Luis; A I Castro; J Baltar; I Baamonde; A Sueiro; M Macias-Gonzalez; D Bellido; F J Tinahones; J A Martinez; F F Casanueva Journal: Int J Obes (Lond) Date: 2017-06-07 Impact factor: 5.095
Authors: Diego Gomez-Arbelaez; Ana B Crujeiras; Ana I Castro; Albert Goday; Antonio Mas-Lorenzo; Ana Bellon; Cristina Tejera; Diego Bellido; Cristobal Galban; Ignacio Sajoux; Patricio Lopez-Jaramillo; Felipe F Casanueva Journal: Endocrine Date: 2017-09-15 Impact factor: 3.633
Authors: Andrea G Izquierdo; Hatim Boughanem; Angel Diaz-Lagares; Isabel Arranz-Salas; Manel Esteller; Francisco J Tinahones; Felipe F Casanueva; Manuel Macias-Gonzalez; Ana B Crujeiras Journal: Epigenetics Date: 2021-07-26 Impact factor: 4.861
Authors: Miriam Nuncia-Cantarero; Sandra Martinez-Canales; Fernando Andrés-Pretel; Gabriel Santpere; Alberto Ocaña; Eva Maria Galan-Moya Journal: Breast Cancer Res Treat Date: 2018-01-12 Impact factor: 4.872