Epigenetic inhibition of nuclear receptor small heterodimer partner is associated with and regulates hepatocellular carcinoma growth.

@article{citeulike:2799344, abstract = {BACKGROUND \& AIMS: Aberrant hypermethylation of promoter regions in cytosine-guanine dinucleotides (CpG) islands has been shown to be associated with transcriptional silencing of tumor-suppressor genes in many cancers. This study evaluated the methylation profile and the tumor-suppressive function of the small heterodimer partner (SHP, NR0B2) in the development of human hepatocellular carcinoma (HCC). METHODS: Human HCC pathologic specimens and cell lines were used as model systems in this study. RESULTS: The expression of SHP is diminished in HCC pathologic specimens and cell lines by epigenetic silencing owing to SHP promoter hypermethylation. In vitro methylation decreased SHP promoter transactivation and nuclear receptor LRH-1 binding, an event that was reversed by demethylation. Overexpression of SHP inhibited HCC foci formation, arrested HCC tumor growth in xenografted nude mice, and increased the sensitivity of HCC cells to apoptotic stimuli. Further analysis of a total of 19 normal liver and 57 HCC specimens showed that down-regulation of SHP gene expression may be a common denominator of HCC. CONCLUSIONS: We propose that SHP functions as a novel tumor suppressor in the development of HCC. These findings provide new insight into the molecular mechanisms leading to this common cancer and may have both diagnostic and therapeutic applications.}, address = {Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.}, author = {He, N. and Park, K. and Zhang, Y. and Huang, J. and Lu, S. and Wang, L. }, citeulike-article-id = {2799344}, doi = {10.1053/j.gastro.2008.01.006}, issn = {1528-0012}, journal = {Gastroenterology}, month = {March}, number = {3}, pages = {793--802}, posted-at = {2008-05-14 16:56:18}, priority = {2}, title = {Epigenetic inhibition of nuclear receptor small heterodimer partner is associated with and regulates hepatocellular carcinoma growth.}, url = {http://dx.doi.org/10.1053/j.gastro.2008.01.006}, volume = {134}, year = {2008} }

TY - JOUR ID - citeulike:2799344 L3 - citeulike-article-id:2799344 TI - Epigenetic inhibition of nuclear receptor small heterodimer partner is associated with and regulates hepatocellular carcinoma growth. JF - Gastroenterology VL - 134 IS - 3 SP - 793 EP - 802 AD - Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA. SN - 1528-0012 N2 - BACKGROUND & AIMS: Aberrant hypermethylation of promoter regions in cytosine-guanine dinucleotides (CpG) islands has been shown to be associated with transcriptional silencing of tumor-suppressor genes in many cancers. This study evaluated the methylation profile and the tumor-suppressive function of the small heterodimer partner (SHP, NR0B2) in the development of human hepatocellular carcinoma (HCC). METHODS: Human HCC pathologic specimens and cell lines were used as model systems in this study. RESULTS: The expression of SHP is diminished in HCC pathologic specimens and cell lines by epigenetic silencing owing to SHP promoter hypermethylation. In vitro methylation decreased SHP promoter transactivation and nuclear receptor LRH-1 binding, an event that was reversed by demethylation. Overexpression of SHP inhibited HCC foci formation, arrested HCC tumor growth in xenografted nude mice, and increased the sensitivity of HCC cells to apoptotic stimuli. Further analysis of a total of 19 normal liver and 57 HCC specimens showed that down-regulation of SHP gene expression may be a common denominator of HCC. CONCLUSIONS: We propose that SHP functions as a novel tumor suppressor in the development of HCC. These findings provide new insight into the molecular mechanisms leading to this common cancer and may have both diagnostic and therapeutic applications. AU - He, N AU - Park, K AU - Zhang, Y AU - Huang, J AU - Lu, S AU - Wang, L PY - 2008/03// UR - http://dx.doi.org/10.1053/j.gastro.2008.01.006 ER -