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Endocrine Abstracts (2017) 49 EP785 | DOI: 10.1530/endoabs.49.EP785

Department of Biochemistry and Biomedicine, University of Sussex, Brighton, UK.


Tumor heterogeneity affects diagnosis, prognosis and response to therapy. Heterogeneity is found in both normal and neoplastic human mammary gland. For example, luminal estrogen receptor (ER)-negative cells can give rise to various phenotypes, including ER-negative and ER-positive mammary tumors, suggesting that the cell-of-origin does not necessarily reflect the tumor type. Regarding ER status, heterogeneity can challenge endocrine therapies; elimination of responsive clones can increase resistance of the survived ones and ultimately reduce treatment efficacy leading to tumor relapse. The aim of our study is to investigate breast tumor heterogeneity and its role in endocrine resistance onset. For this purpose, we co-cultured ER-positive (T47D, CAMA1) and triple negative breast cancer (TNBC) (MDA-MB231, HCC70) cell lines, using 2D and 3D models. CAMA1 were sensitive to tamoxifen in term of cell viability, however this sensitivity was reduced when CAMA1 were co-cultured with TNBC cells. Interestingly, following co-culture with TNBC cells, the expression of ER in CAMA1 decreased while the anti-apoptotic protein Mcl-1 increased. On the other hand, T47D are slightly sensitive to tamoxifen; however, this sensitivity was completely abolished when T47D were co-cultured with TNBC. In addition, the expression of ER in T47D was significantly increased following co-culturing with TNBC cells, while the doubling-time of T47D was significantly reduced, suggesting an increase in cell proliferation rate. Our results demonstrate that ER status appears to be modulated when ER positive cells are co-cultured with TNBC cells, leading to a different response to endocrine therapy. In addition, ER positive cells’ doubling time is modified after exposure to TNBC cells. Further experiments are needed to fully understand the molecular mechanisms behind these findings.

Volume 49

19th European Congress of Endocrinology

Lisbon, Portugal
20 May 2017 - 23 May 2017

European Society of Endocrinology 

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