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Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells
- Source :
- Oncotarget, Oncotarget 8 (2017): 109000–109017. doi:10.18632/oncotarget.22552, info:cnr-pdr/source/autori:Ambrosio M.R.; D'Esposito V.; Costa V.; Liguoro D.; Collina F.; Cantile M.; Prevete N.; Passaro C.; Mosca G.; De Laurentiis M.; Di Bonito M.; Botti G.; Franco R.; Beguinot F.; Ciccodicola A.; Formisano P./titolo:Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells/doi:10.18632%2Foncotarget.22552/rivista:Oncotarget/anno:2017/pagina_da:109000/pagina_a:109017/intervallo_pagine:109000–109017/volume:8
- Publication Year :
- 2017
- Publisher :
- Impact Journals LLC, 2017.
-
Abstract
- // Maria Rosaria Ambrosio 1, * , Vittoria D’Esposito 1, * , Valerio Costa 2 , Domenico Liguoro 1 , Francesca Collina 3 , Monica Cantile 3 , Nella Prevete 1 , Carmela Passaro 1 , Giusy Mosca 1 , Michelino De Laurentiis 4 , Maurizio Di Bonito 3 , Gerardo Botti 3 , Renato Franco 5 , Francesco Beguinot 1 , Alfredo Ciccodicola 2, 6 and Pietro Formisano 1 1 Department of Translational Medicine, University of Naples “Federico II” & URT “Genomic of Diabetes” of Institute of Experimental Endocrinology and Oncology “G. Salvatore”, National Council of Research (CNR), Naples 80131, Italy 2 Institute of Genetic and Biophysics “A. Buzzati-Traverso”, CNR, Naples 80131, Italy 3 Pathology Unit, National Cancer Institute “G. Pascale Foundation”, Naples 80131, Italy 4 Department of Breast Surgery and Cancer Prevention, National Cancer Institute “G. Pascale Foundation”, Naples 80131, Italy 5 Pathology Unit, Universita degli Studi della Campania “Luigi Vanvitelli”, Naples 80138, Italy 6 Department of Science and Technology, University of Naples “Parthenope”, Naples 80131, Italy * These authors have equally contributed to this work Correspondence to: Pietro Formisano, email: fpietro@unina.it Keywords: breast cancer; tamoxifen; glucose; adipose tissue; connective tissue growth factor Received: April 21, 2017 Accepted: July 25, 2017 Published: November 20, 2017 ABSTRACT Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Adipose tissue
Connective tissue
Estrogen receptor
03 medical and health sciences
0302 clinical medicine
Breast cancer
breast cancer
Internal medicine
medicine
connective tissue growth factor
glucose
skin and connective tissue diseases
Cancer prevention
tamoxifen
business.industry
Cancer
medicine.disease
adipose tissue
CTGF
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Oncology
030220 oncology & carcinogenesis
business
Tamoxifen
medicine.drug
Research Paper
Subjects
Details
- Language :
- English
- ISSN :
- 19492553
- Volume :
- 8
- Issue :
- 65
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....38f6882fb3453e49ea69498566f2b3bd