Promoting E2F1-mediated apoptosis in oestrogen receptor-alpha-negative breast cancer cells

作者：Montenegro Maria F^*; del Mar Collado Gonzalez Maria; Piedad Fernandez Perez Maria; Hammouda Manel B; Tolordava Lana; Gamkrelidze Mariam; Neptuno Rodriguez Lopez Jose

来源：BMC Cancer, 2014, 14(1): 539.

DOI：10.1186/1471-2407-14-539

• Breast cancer
• Oestrogen receptor alpha
• E2F1
• 4-Hydroxy-tamoxifen
• Apoptosis

Background: Because oestrogen receptor a (ER alpha) regulates E2F1 expression to mediate tamoxifen resistance in ER alpha-positive breast cancer cells, we aimed to define the possible roles of ER alpha and E2F1 in promoting the resistance of ER alpha-negative breast cancer cells to 4-hydroxy-tamoxifen (4OHT). %26lt;br%26gt;Methods: This study utilised conventional techniques to demonstrate the effects of 4OHT on the expression of ER alpha and E2F1 and also examined the individual and combined effects of 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG) on the oestrogen-negative MDA-MB-231 breast cancer cell line using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and confocal microscopy. %26lt;br%26gt;Results: Despite the ER alpha-negative status of the MDA-MB-231 cells, we observed that 4OHT efficiently up-regulated ER alpha in these cells and that this upregulation promoted E2F1-mediated cell growth. Because E2F1 plays a dual role in cell growth/apoptosis, we designed a therapy incorporating TMCG/DIPY to take advantage of the elevated E2F1 expression in these 4OHT-treated cells. 4OHT enhances the toxicity of TMCG/DIPY in these ER alpha-negative breast cancer cells. %26lt;br%26gt;Conclusions: Because TMCG/DIPY treatment modulates the methylation status/stability of E2F1, the results demonstrate that therapies targeting the epigenetic machinery of cancer cells in the presence of overexpressed E2F1 may result in efficient E2F1-mediated cell death.

• 出版日期2014-7-26