Oncotarget

Research Papers:

Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells

Maria Rosaria Ambrosio, Vittoria D’Esposito, Valerio Costa, Domenico Liguoro, Francesca Collina, Monica Cantile, Nella Prevete, Carmela Passaro, Giusy Mosca, Michelino De Laurentiis, Maurizio Di Bonito, Gerardo Botti, Renato Franco, Francesco Beguinot, Alfredo Ciccodicola and Pietro Formisano _

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2017; 8:109000-109017. https://doi.org/10.18632/oncotarget.22552

Metrics: PDF 1412 views  |   HTML 3179 views  |   ?  


Abstract

Maria Rosaria Ambrosio1,*, Vittoria D’Esposito1,*, Valerio Costa2, Domenico Liguoro1, Francesca Collina3, Monica Cantile3, Nella Prevete1, Carmela Passaro1, Giusy Mosca1, Michelino De Laurentiis4, Maurizio Di Bonito3, Gerardo Botti3, Renato Franco5, Francesco Beguinot1, Alfredo Ciccodicola2,6 and Pietro Formisano1

1Department 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

2Institute of Genetic and Biophysics “A. Buzzati-Traverso”, CNR, Naples 80131, Italy

3Pathology Unit, National Cancer Institute “G. Pascale Foundation”, Naples 80131, Italy

4Department of Breast Surgery and Cancer Prevention, National Cancer Institute “G. Pascale Foundation”, Naples 80131, Italy

5Pathology Unit, Università degli Studi della Campania “Luigi Vanvitelli”, Naples 80138, Italy

6Department of Science and Technology, University of Naples “Parthenope”, Naples 80131, Italy

*These authors have equally contributed to this work

Correspondence to:

Pietro Formisano, email: [email protected]

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.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 22552