- Meeting abstract
- Open Access
Investigating the functional role of the oestrogen receptor in LY2 endocrine resistant breast cancer cells
© Ramkaran et al. 2015
Published: 27 October 2015
The issue of acquired resistance to breast cancer regimes such as tamoxifen continues to negatively affect clinical outcomes. While many mechanisms of resistance have been discovered [1, 2], there is evidence now of acquired resistance through adaptation of the oestrogen receptor itself leading to tumour progression . A thorough understanding of the processes involved in the receptor's adaptation remains unclear. This study gives evidence of the gene signalling which shed light on the mechanism of adaptation in an LY2 endocrine resistant cell line oestrogen receptor knockdown model.
Real time PCR examines the gene expression profile of the LY2 cells under various treatments including oestrogen, tamoxifen and a mixture of both.
It was found that the normal oestrogen receptor target genes PS2 and GREB1 display reduced expression without the presence of the receptor. However EGR3 signals excessively despite having the receptor stably knockdown.
As a result these data provides evidence that EGR3 is involved in the adaptation of the oestrogen receptor and that global signalling of common target genes does not occur when the receptor adapts. Hence it demonstrates an initial clue of the process of adaptation in resistant tumours that have changed their receptor status.
- García-Becerra R, Santos N, Díaz L, Camacho J: Mechanisms of Resistance to Endocrine Therapy in Breast Cancer: Focus on Signaling Pathways, miRNAs and Genetically Based Resistance. Int J Mol Sci. 2012, 14 (1): 108-145. 10.3390/ijms14010108.PubMedPubMed CentralView ArticleGoogle Scholar
- Normanno N, Di Maio M, De Maio E, De Luca A, de Matteis A, Giordano A, et al: Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Cancer. 2005, 12 (4): 721-747. 10.1677/erc.1.00857.PubMedView ArticleGoogle Scholar
- Vareslija D MJ, Fagan A, Redmond A M, Hao Y, O'Gaora P, Hill ADK, Young LS: Adaptation to AI therapy in breast cancer can induce dynamic alterations in ER activity resulting in estrogen independent metastatic tumours. Clinical Cancer Research.Google Scholar
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