دورية أكاديمية
COX-2 promotes mammary adipose tissue inflammation, local estrogen biosynthesis, and carcinogenesis in high-sugar/fat diet treated mice.
العنوان: | COX-2 promotes mammary adipose tissue inflammation, local estrogen biosynthesis, and carcinogenesis in high-sugar/fat diet treated mice. |
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المؤلفون: | Gonçalves RM; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Delgobo M; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Agnes JP; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., das Neves RN; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Falchetti M; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Casagrande T; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Garcia APV; Laboratório de Patologia Comparada, Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Minas Gerais, Brazil., Vieira TC; Laboratório de Patologia Comparada, Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Minas Gerais, Brazil., Somensi N; Centro de Estudos em Estresse Oxidativo (CEEO), Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, 90035-003, Brazil., Bruxel MA; Laboratório de Investigação de Doenças Crônicas (LIDoC), Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Mendes DAGB; Laboratório de Imunobiologia (LIDI), Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Rafacho A; Laboratório de Investigação de Doenças Crônicas (LIDoC), Departamento de Ciências Fisiológicas, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Báfica A; Laboratório de Imunobiologia (LIDI), Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil., Gelain DP; Centro de Estudos em Estresse Oxidativo (CEEO), Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, 90035-003, Brazil., Moreira JCF; Centro de Estudos em Estresse Oxidativo (CEEO), Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, 90035-003, Brazil., Cassali GD; Laboratório de Patologia Comparada, Departamento de Patologia Geral, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, 31270-901, Minas Gerais, Brazil., Bishop AJR; Greehey Children's Cancer Research Institute, University of Texas Health at San Antonio, San Antonio, TX, 78229, USA., Zanotto-Filho A; Laboratório de Farmacologia e Bioquímica do Câncer (LabCancer), Departamento de Farmacologia, Universidade Federal de Santa Catarina (UFSC), Florianópolis, Santa Catarina, 88049-900, Brazil. Electronic address: alfeu.zanotto@ufsc.br. |
المصدر: | Cancer letters [Cancer Lett] 2021 Apr 01; Vol. 502, pp. 44-57. Date of Electronic Publication: 2021 Jan 09. |
نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: Elsevier Science Ireland Country of Publication: Ireland NLM ID: 7600053 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-7980 (Electronic) Linking ISSN: 03043835 NLM ISO Abbreviation: Cancer Lett Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Limerick : Elsevier Science Ireland Original Publication: Amsterdam, Elsevier/North-Holland. |
مواضيع طبية MeSH: | Up-Regulation*, Breast Neoplasms/*metabolism , Cyclooxygenase 2/*metabolism , Diet, High-Fat/*adverse effects , Dinoprostone/*biosynthesis , Sugars/*adverse effects, 9,10-Dimethyl-1,2-benzanthracene/adverse effects ; Animals ; Aromatase/metabolism ; Breast Neoplasms/chemically induced ; Breast Neoplasms/drug therapy ; Cell Line, Tumor ; Chemokine CCL2/metabolism ; Disease Models, Animal ; Etoricoxib/administration & dosage ; Etoricoxib/pharmacology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Interleukin-6/metabolism ; MCF-7 Cells ; Medroxyprogesterone Acetate/adverse effects ; Mice |
مستخلص: | Obesity is a major risk factor for breast cancer, especially in post-menopausal women. In the breast tissue of obese women, cyclooxygenase-2 (COX-2)-dependent prostaglandin E2 (PGE2) production has been correlated with inflammation and local estrogen biosynthesis via aromatase. Using a mouse model of 7,12-dimethylbenz[a]anthracene/medroxyprogesterone-acetate (DMBA/MPA)-induced carcinogenesis, we demonstrated that an obesogenic diet promotes mammary tissue inflammation and local estrogen production, and accelerates mammary tumor formation in a COX-2-dependent manner. High-sugar/fat (HSF) diet augmented the levels of the pro-inflammatory mediators MCP-1, IL-6, COX-2, and PGE2 in mammary tissue, and this was accompanied by crown-like structures of breast (CLS-B) formation and aromatase/estrogen upregulation. Treatment with a COX-2 selective inhibitor, etoricoxib, decreased PGE2, IL-6, MCP-1, and CLS-B formation as well as reduced aromatase protein and estrogen levels in the mammary tissue of mice fed a HSF diet. Etoricoxib-treated mice showed increased latency and decreased incidence of mammary tumors, which resulted in prolonged animal survival when compared to HSF diet alone. Inhibition of tumor angiogenesis also seemed to account for the prolonged survival of COX-2 inhibitor-treated animals. In conclusion, obesogenic diet-induced COX-2 is sufficient to trigger inflammation, local estrogen biosynthesis, and mammary tumorigenesis. (Copyright © 2021 Elsevier B.V. All rights reserved.) |
فهرسة مساهمة: | Keywords: Aromatase; Crown-like structures; Cyclooxygenase-2; Cytokines; Prostaglandin E2 |
المشرفين على المادة: | 0 (CCL2 protein, human) 0 (Chemokine CCL2) 0 (IL6 protein, human) 0 (Interleukin-6) 0 (Sugars) 57-97-6 (9,10-Dimethyl-1,2-benzanthracene) C2QI4IOI2G (Medroxyprogesterone Acetate) EC 1.14.14.1 (Aromatase) EC 1.14.99.1 (Cyclooxygenase 2) EC 1.14.99.1 (PTGS2 protein, human) K7Q1JQR04M (Dinoprostone) WRX4NFY03R (Etoricoxib) |
تواريخ الأحداث: | Date Created: 20210111 Date Completed: 20210804 Latest Revision: 20210804 |
رمز التحديث: | 20221213 |
DOI: | 10.1016/j.canlet.2021.01.003 |
PMID: | 33429006 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1872-7980 |
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DOI: | 10.1016/j.canlet.2021.01.003 |