Diabetes mellitus potentiates the risk of breast cancer. We have previously described the pro-tumorigenic effects of advanced glycation end-products (AGEs) on estrogen receptor (ER)-negative MDA-MB-231 breast cancer cell line mediated through the receptor for AGEs (RAGE). However, a predominant association between women with ER-positive breast cancer and type 2 diabetes mellitus has been reported. Therefore, we have investigated the biological impacts of AGEs on ER-positive human breast cancer cell line MCF-7 using in vitro cell-based assays including cell count, migration, and invasion assays. Western blot, FACS analyses and quantitative real time-PCR were also performed. We found that AGEs at 50-100 g/mL increased MCF-7 cell proliferation and cell migration associated with an enhancement of pro-matrix metalloproteinase (MMP)-9 activity, without affecting their poor invasiveness. However, 200 g/mL AGEs inhibited MCF-7 cell proliferation through induction of apoptosis indicated by caspase-3 cleavage detected using Western blotting. A phospho-protein array analysis revealed that AGEs mainly induce the phosphorylation of extracellular-signal regulated kinase (ERK)1/2 and cAMP response element binding protein-1 (CREB1), both signaling molecules considered as key regulators of AGEs pro-tumorigenic effects. We also showed that AGEs up-regulate RAGE and ER expression at the protein and transcript levels in MCF-7 cells, in a RAGE-dependent manner after blockade of AGEs/RAGE interaction using neutralizing anti-RAGE antibody. Throughout the study, BSA had no effect on cellular processes. These findings pave the way for future studies investigating whether the exposure of AGEs-treated ER-positive breast cancer cells to estrogen could lead to a potentiation of the breast cancer development and progression.
Dr.Sabine Matou-Nasri, research scientist at King Abdullah Medical Research Center (KAIMRC), is leading the Cell and Gene Therapy group, part of Medical Genomics Research Department. She obtained her PhD degree in Biological and Medical Engineering in first class honors with distinction at University of Paris 13, Paris, France. She had her post-doctoral training at the School of Healthcare Science, Manchester Metropolitan University, Manchester, United Kingdom.
During her PhD and first post-doctoral training, she established structure-function relationships of sulfated polysaccharides (extracted from brown seaweeds) endowed with anticoagulant, antithrombotic and pro-angiogenic properties. She ended up with an international patent.
Since she has been at KAIMRC, her work is focused on various medical fields related to cancer (lymphoma, leukemia, and breast cancer), diabetes, inflammatory disease (gastritis) and infectious diseases (MERS-CoV). Her main aim is to pinpoint cancer-specific biomarkers and to investigate the anticancer effects of phytochemical compounds.
She has been active in research with 32 peer-reviewed publications in Biochimica and Biophysica Acta, Scientific Reports for instance, and several research grants as a principal investigator and as a co-investigator. She has also co-supervised and supervised 8 MSc, 5 PhD students, and 1 postdoctoral fellow.