期刊
ENDOCRINE
卷 36, 期 2, 页码 224-232出版社
HUMANA PRESS INC
DOI: 10.1007/s12020-009-9233-8
关键词
ER beta; Microarray; HEK293; Target gene; Chromatin immunoprecipitation
资金
- Swedish Cancer Fund
Estrogen receptors (ERs), ER alpha and ER beta, mediate estrogen actions in a broad range of target tissues. With the introduction of microarray techniques, a significant understanding has been gained regarding the interplay between the ER alpha and ER beta in breast cancer cell lines. To gain a more comprehensive understanding of ER beta-dependent gene regulation independent of ER alpha, we performed microarray analysis on HEK293/mock and HEK293/ER beta cells. A total of 332 genes was identified as ER beta-upregulated genes and 210 identified as ER beta-downregulated genes. ER beta-induced and ER beta-repressed genes were involved in cell-cell signaling, morphogenesis, and cell proliferation. The ER beta repressive effect on genes related to proliferation was further studied by proliferation assays, where ER beta expression resulted in a significant decrease in cell proliferation. To identify primary ER beta target genes, we examined a number of ER beta-regulated genes using chromatin immunoprecipitation assays for regions bound by ER beta. Our results showed that ER beta recruitment was significant to regions associated with 12 genes (IL1RAP, TMSB4X, COLEC12, ENPP2, KLRC1, RERG, RGS16, TNNT2, CYR61, FER1L3, FAM108A1, and CYP4X1), suggesting that these genes are likely to be ER beta primary target genes. This study has provided novel information on the gene regulatory function of ER beta independent of ER alpha and identified a number of ER beta primary target genes. The results of Gene Ontology analysis and proliferation assays are consistent with an antiproliferative role of ER beta independent of ER alpha.
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