Anna Sanchez1,2, Frédérique Penault-Llorca2,3, Yves-Jean Bignon1,2, Laurent Guy2,4, Dominique Bernard-Gallon5,2. 1. Department of Oncogenetics, Centre Jean Perrin, Clermont-Ferrand, France. 2. INSERM U 1240 Molecular Imagery and Theranostic Strategies (IMoST), Clermont-Ferrand, France. 3. Department of Biopathology, Centre Jean Perrin, Clermont-Ferrand, France. 4. Department of Urology, Gabriel Montpied Hospital, Clermont-Ferrand, France. 5. Department of Oncogenetics, Centre Jean Perrin, Clermont-Ferrand, France; dominique.gallon-bernard@clermont.unicancer.fr.
Abstract
BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. MATERIALS AND METHODS: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. RESULTS: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. CONCLUSION: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth. Copyright
BACKGROUND/AIM: Histone methylation status is required to control gene expression. H3K27me3 is an epigenetic tri-methylation modification to histone H3 controlled by the demethylase JMJD3. JMJD3 is dysregulated in a wide range of cancers and has been shown to control the expression of a specific growth-modulatory gene signature, making it an interesting candidate to better understand prostate tumor progression in vivo. This study aimed to identify the impact of JMJD3 inhibition by its inhibitor, GSK4, on prostate tumor growth in vivo. MATERIALS AND METHODS: Prostate cancer cell lines were implanted into Balb/c nude male mice. The effects of the selective JMJD3 inhibitor GSK-J4 on tumor growth were analyzed by bioluminescence assays and H3K27me3-regulated changes in gene expression were analyzed by ChIP-qPCR and RT-qPCR. RESULTS: JMJD3 inhibition contributed to an increase in tumor growth in androgen-independent (AR-) xenografts and a decrease in androgen-dependent (AR+). GSK-J4 treatment modulated H3K27me3 enrichment on the gene panel in DU-145-luc xenografts while it had little effect on PC3-luc and no effect on LNCaP-luc. Effects of JMJD3 inhibition affected the panel gene expression. CONCLUSION: JMJD3 has a differential effect in prostate tumor progression according to AR status. Our results suggest that JMJD3 is able to play a role independently of its demethylase function in androgen-independent prostate cancer. The effects of GSK-J4 on AR+ prostate xenografts led to a decrease in tumor growth. Copyright
Authors: H Zhong; F Agani; A A Baccala; E Laughner; N Rioseco-Camacho; W B Isaacs; J W Simons; G L Semenza Journal: Cancer Res Date: 1998-12-01 Impact factor: 12.701
Authors: Laurens Kruidenier; Chun-wa Chung; Zhongjun Cheng; John Liddle; KaHing Che; Gerard Joberty; Marcus Bantscheff; Chas Bountra; Angela Bridges; Hawa Diallo; Dirk Eberhard; Sue Hutchinson; Emma Jones; Roy Katso; Melanie Leveridge; Palwinder K Mander; Julie Mosley; Cesar Ramirez-Molina; Paul Rowland; Christopher J Schofield; Robert J Sheppard; Julia E Smith; Catherine Swales; Robert Tanner; Pamela Thomas; Anthony Tumber; Gerard Drewes; Udo Oppermann; Dinshaw J Patel; Kevin Lee; David M Wilson Journal: Nature Date: 2012-08-16 Impact factor: 49.962