Estrogen receptor isoform-specific regulation of endogenous gene expression in human osteoblastic cell lines expressing either ER? or ER?
| Autor: | Steven A. Johnsen, David G. Monroe, B. Lawrence Riggs, Sundeep Khosla, Thomas C. Spelsberg, Barbara Getz |
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| Rok vydání: | 2003 |
| Předmět: |
Gene isoform
Transcription Genetic Cellular differentiation Estrogen receptor Bone Neoplasms Biology Biochemistry Gene expression Tumor Cells Cultured polycyclic compounds Estrogen Receptor beta Humans Protein Isoforms RNA Messenger RNA Neoplasm Molecular Biology Estrogen receptor beta Oligonucleotide Array Sequence Analysis Regulation of gene expression Osteosarcoma Estradiol Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Estrogen Receptor alpha Cell Differentiation Cell Biology Molecular biology Anti-Bacterial Agents Gene expression profiling Gene Expression Regulation Receptors Estrogen Doxycycline Estrogen receptor alpha Cell Division hormones hormone substitutes and hormone antagonists |
| Zdroj: | Journal of Cellular Biochemistry. 90:315-326 |
| ISSN: | 1097-4644 0730-2312 |
| DOI: | 10.1002/jcb.10633 |
| Popis: | Estrogen (17beta-estradiol, E2) plays pivotal roles in the function and maintenance of the skeleton, including the bone-forming osteoblasts (OBs). The functions of E2 are largely mediated through two distinct estrogen receptor isoforms, ERalpha and ERbeta, both of which are expressed in OBs. The level of each isoform dominates at early or late stages of OB differentiation. To date, only a limited comparison between the transcriptional targets of ERalpha and ERbeta on endogenous gene expression has been reported. We have developed new stable cell lines, which contain doxycycline (Dox)-inducible ERalpha and ERbeta, in the U2OS human osteosarcoma to determine the global transcriptional profile of ERalpha- and ERbeta-regulation of endogenous gene expression. The U2OS-ERalpha and U2OS-ERbeta cell lines were treated with Dox and either vehicle control or E2 for 24 h. Gene expression analysis was performed using a microarray containing approximately 6,800 full-length genes. We detected 63 genes that were regulated solely by ERalpha and 59 genes that were only regulated solely by ERbeta. Of the ERalpha-regulated genes, 81% were upregulated and 19% were inhibited. Similarly 76% of the ERbeta-regulated genes were upregulated whereas 24% were inhibited by E2. Surprisingly, only 17 genes were induced by both ERalpha and ERbeta. Real-time PCR was employed to confirm the expression of a selected number of genes. The regulation of a number of known E2-responsive genes in human OBs, as well as many interesting novel genes, is shown. The distinct patterns of E2-dependent gene regulation in the U2OS cells by ERalpha and ERbeta shown here suggest that during OB differentiation, when either isoform dominates, a unique pattern of gene responses will occur, partially due to the differentiation state and the ER isoform present. |
| Databáze: | OpenAIRE |
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