Profiling of selenomethionine responsive genes in colon cancer by microarray analysis.

TitleProfiling of selenomethionine responsive genes in colon cancer by microarray analysis.
Publication TypeJournal Article
Year of Publication2007
AuthorsGoulet A-C, Watts G, Lord JL, Nelson MA
JournalCancer Biol Ther
Volume6
Issue4
Pagination494-503
Date Published2007 Apr
ISSN1538-4047
KeywordsCell Line, Tumor, Chromatin, Colonic Neoplasms, Connexin 26, Connexins, Gene Expression, Gene Expression Profiling, Genes, Neoplasm, Histones, Humans, Immediate-Early Proteins, Oligonucleotide Array Sequence Analysis, Promoter Regions, Genetic, Protein-Serine-Threonine Kinases, Selenomethionine
Abstract

High-selenium containing yeast is being evaluated in clinical trials against colon polyp recurrence. However, the molecular targets for the anticancer effects of selenium remain unclear. Previous studies by our group demonstrated that selenomethionine-induced growth arrest appears to be mediated by activation of ERK and subsequent phosphorylation of RSK and histone H3. These results suggest that selenomethionine can alter gene expression. In the present study, we have used cDNA microarrays to determine whether gene expression differences exist in HCT116 colon cancer cells treated with selenomethionine. These experiments reveal statistically significant expression changes for 50 genes. Genes we found to increase with selenomethionine treatment include KLK6, ATOX1, SGK, GJB2, DAP-1, PLAU, VIM, DPYSL2, STC2 and PXN. Conversely, genes downregulated by selenomethionine include PRKACB, LIM, DEPP, MYC, CDH5, ELF3, VSNL1, SAT and EGLN3. Further analysis of those genes using chromatin immunoprecipitation experiments showed that phosphorylated histone H3 on serine 10 bound to the GJB2 promoter (connexin 26) or the serum glucocorticoid kinase promoter is increased with selenomethionine treatment. Cells overexpressing CX26 or DAP-1 displayed a reduced number of colonies which suggests that these two genes could play a functional role in the growth inhibitory effects of selenomethionine. These data support the notion that selenomethionine-induced growth inhibition is associated with global changes in gene expression. They also demonstrate that selenomethionine can modify chromatin state to alter gene transcription. Finally, our studies provide a practical foundation for the further development of biomarkers to monitor the efficacy of selenomethionine in clinical trials.

Alternate JournalCancer Biol. Ther.
PubMed ID17374985
Grant ListCA72008 / CA / NCI NIH HHS / United States
P30 CA023074 / CA / NCI NIH HHS / United States
ES06694 / ES / NIEHS NIH HHS / United States
P30 ES006694 / ES / NIEHS NIH HHS / United States
CA23074 / CA / NCI NIH HHS / United States
CA97383 / CA / NCI NIH HHS / United States
Faculty Member Reference: 
George Watts, Ph.D.