Estrogen receptor beta signalling is potentiated by coactivators p300 and CBP in PC3 prostate cancer cells

Konference: 2009 5. sympózium a workshop molekulární patologie a histo-cyto-chemie

Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie

Téma: Postery

Číslo abstraktu: p002

Autoři: Mgr. Jan Bouchal; H. Neuwirt; F.R. Santer; Z. Culig

Introduction: It has been demonstrated that increased expressions of p300 and CBP coactivators in prostate cancer contribute to androgen independent proliferation. The aim of this project was to investigate the relevance of the coactivators for estrogen receptor beta (ER beta) - mediated transcription in prostate cancer.

Materials and methods: Luciferase assays were performed in PC3 cells after transfection with ERE reporter and vectors affecting the expression of p300/CBP (expression vectors for both p300 and CBP, siRNAs against both p300 and CBP). Luciferase activity was assessed after stimulation of ER beta by genistein alone and in combination with ER antagonists ICI 182 780 or ICI 164 384.

Results: Stimulation of ER beta with 1000 nM genistein was further potentiated by acquired p300 or CBP expression in PC3 cells. The stimulation was abolished by 100 nM ICI 182 780 or 1000 nM ICI 164 384. Anti-estrogens exerted no agonistic effects on ER beta in the presence of either p300 or CBP. Knockdown of p300 and CBP by specific siRNAs abolished genistein stimulation of ER beta. The impact of p300/CBP coactivators on proliferation and apoptosis of PC3 cells after genistein treatment is currently being investigated. Other prostate cancer cell lines (DU145, LNCaP, LNCaP-abl, C4-2) were similarly tested. However, the luciferase signals were very low, probably due to low levels of the ER beta receptor.

Discussion: Coactivators p300 and CBP, which are both increased in advanced prostate cancers, potentiate signalling via ER beta. This might be important in tailored treatment with ER beta ligands.

The work was supported by MSM 6198959216, Aktion 2007 and 2008 (49p6 and 51p19, www.dzs.cz) and travel grants from www.uicc.org (ICR-06-041, 2006) and www.oead.at (Ernst Mach, 2007).

Datum přednesení příspěvku: 24. 4. 2009