FP07-4 A Positive Feedback Mechanism Between Estrogen and Tnfα in An ER+ Breast Tumour Microenvironment

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP07-New Players in Hormonal Control of Breast & Prostate Cancer
Saturday, June 15, 2013: 11:00 AM-11:30 AM
Presentation Start Time: 11:45 AM
Room 206 (Moscone Center)

Poster Board SAT-294
Sarah Quynh Giao To*1, Kevin Christopher Knower2 and Colin D Clyne3
1Prince Henry's Institute, Clayton, Australia, 2Prince Henry's Institute, Melbourne, Australia, 3Prince Henry's Institute, Clayton VIC, Australia
TNFα plays a critical role in estrogen receptor positive (ER+) breast cancer pathology. It serves as an anti-adipogenic factor, responsible for maintaining adjacent cancer-associated fibroblasts in an undifferentiated state. TNFα also increases the transcription or activity of key estrogen-producing enzymes in these cells. There are high levels of TNFα detected within the tumour microenvironment, and though infiltrating immune cells are thought to contribute a significant amount of TNFα, the relative role of the ER+ tumour epithelial cells in producing this cytokine as a tumour-derived paracrine signalling factor has not been examined. The aim of this study was to determine the relative contribution of tumour epithelial cells to TNFα production and how this is regulated by examining a number of breast cancer cell lines. Analysis of relative mRNA and secretion levels revealed that the ER- cell line HS578t contained the highest concentrations of TNFα, whilst the ER+ cell lines T47D and MCF7 showed the lowest concentration. Treatment of MCF7 cells with estradiol increased TNFα transcript within 6hrs of treatment and secretion within 24hrs, an effect which was mitigated when the ERα antagonist ICI 182,780 was additionally added. Expression of the TNFR1 receptor was not increased by estradiol treatment in breast cancer cells. Our findings have established a novel way in which SERM therapy combats ER+ breast tumours. By blockade of the estrogen receptor, TNFα production in tumour cells in response to estradiol is diminished. This reduces the capacity of tumours to maintain the surrounding dense layer of undifferentiated fibroblasts, and also lowers its estrogens-producing potential. TNFα has many roles in breast cancer pathology, and breaking the positive cycle of its production and action within an ER+ breast tumour microenvironment is critical for successful clinical outcomes.

Nothing to Disclose: SQGT, KCK, CDC

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm