Aberrant transforming growth factor beta1 signaling and SMAD4 nuclear translocation confer epigenetic repression of ADAM19 in ovarian cancer.

Neoplasia : an International Journal for Oncology Research
Michael W Y ChanHuey-Jen L Lin

Abstract

Transforming growth factor-beta (TGF-beta)/SMAD signaling is a key growth regulatory pathway often dysregulated in ovarian cancer and other malignancies. Although loss of TGF-beta-mediated growth inhibition has been shown to contribute to aberrant cell behavior, the epigenetic consequence(s) of impaired TGF-beta/SMAD signaling on target genes is not well established. In this study, we show that TGF-beta1 causes growth inhibition of normal ovarian surface epithelial cells, induction of nuclear translocation SMAD4, and up-regulation of ADAM19 (a disintegrin and metalloprotease domain 19), a newly identified TGF-beta1 target gene. Conversely, induction and nuclear translocation of SMAD4 were negligible in ovarian cancer cells refractory to TGF-beta1 stimulation, and ADAM19 expression was greatly reduced. Furthermore, in the TGF-beta1 refractory cells, an inactive chromatin environment, marked by repressive histone modifications (trimethyl-H3K27 and dimethyl-H3K9) and histone deacetylase, was associated with the ADAM19 promoter region. However, the CpG island found within the promoter and first exon of ADAM19 remained generally unmethylated. Although disrupted growth factor signaling has been linked to epigenetic gene silencing in ...Continue Reading

Citations

Jul 4, 2009·Endocrinology·Curt BalchKenneth P Nephew
Aug 13, 2010·Biomarkers in Medicine·Leonel Maldonado, Mohammad Obaidul Hoque
Aug 28, 2020·Molecular and Cellular Biochemistry·Yanhua JiangLinlin Chen
Feb 18, 2014·Molecular Biology Reports·Ning-Sheng LaiMichael W Y Chan
May 5, 2011·Epigenetics : Official Journal of the DNA Methylation Society·Kun-Tu YehMichael W Y Chan
Jun 4, 2015·Proceedings of the National Academy of Sciences of the United States of America·Premalatha ShathasivamTheodore J Brown
May 5, 2011·International Journal of Molecular Sciences·Mi Jeong Kwon, Young Kee Shin
Jul 9, 2014·Oncotarget·Fang FangKenneth P Nephew
Oct 15, 2019·Frontiers in Cell and Developmental Biology·Alka SinghManisha Sachan
Jan 13, 2010·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jian-Liang ChouMichael W-Y Chan
Sep 2, 2014·International Journal of Oncology·Chia-Ming YehMichael W Y Chan
Mar 2, 2017·The Journal of Pathology·Angela Rynne-VidalManuel López-Cabrera
Jul 21, 2009·BMC Systems Biology·Huaxia QinRamana V Davuluri

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