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Estrogen receptor regulates insulin-like growth factor-I receptor gene expression in breast tumor cells: involvement of transcription factor Sp1.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Maor, Sharon Mayer, Doris Yarden, Ronit I. Lee, Adrian V. Sarfstein, Rive Werner, Haim Papa, Moshe Zvi |
| Copyright Year | 2006 |
| Abstract | The insulin-like growth factors, IGF-I and IGF-II are a family of mitogenic polypeptides with important roles in growth and differentiation. The biological actions of the IGFs are mediated by the IGF-I receptor (IGF-IR), a cell-surface tyrosine kinase, whose activation by serum IGF-I seems to be a key step in breast cancer initiation. Evidence accumulated indicates that estrogens stimulate the expression and activity of IGF axis components. The aim of our study was to examine the transcriptional mechanisms involved in regulation of IGF-IR gene expression by the estrogen receptor (ER). For this purpose, transient transfections using an IGF-IR promoter-luciferase reporter plasmid were performed in breast cancer-c derived ER-positive MCF-7 cells and isogenic ER-negative C4 cells. To examine the potential involvement of zinc-finger nuclear proteins in the transactivating effect of estrogens, chromatin immunoprecipitation (ChIP) experiments were performed using an Sp1 antibody, along with the Sp1-family-binding inhibitor Mithramycin A. The results obtained indicate that basal IGF-IR promoter activity was 5.8-fold higher in MCF-7 than in C4 cells. Estradiol treatment significantly activated the IGF-IR promoter in MCF-7, but not in C4 cells. Furthermore, the estrogen responsive region in the IGF-IR promoter was mapped to a GC-rich sequence located between nucleotides -40 and -188 in the 5' flanking region. ChIP experiments revealed that at least part of the estrogen effect on IGF-IR expression was mediated through activation of the Sp1 transcription factor. In summary, our studies demonstrate that IGF-IR gene transcription in breast cancer cells is controlled by interactions between ERalpha and Sp1. Dysregulated expression of the IGF-IR gene may have pathologic consequences with relevance in breast cancer etiology. |
| Starting Page | 621 |
| Ending Page | 626 |
| Page Count | 6 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://intl-joe.endocrinology-journals.org/content/191/3/605.full.pdf |
| PubMed reference number | 17170218v1 |
| Volume Number | 191 |
| Issue Number | 3 |
| Journal | The Journal of endocrinology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | 5' Flanking Region Axis vertebra Cancer Etiology Estradiol Estrogen Receptor alpha Estrogen Receptors Estrogens Flank (surface region) Gene Expression IGF2R protein, human Luciferases Mammary Neoplasms Nucleotides Polypeptides Protein Tyrosine Kinase Somatomedins TRANSCRIPTION FACTOR Transcription Initiation Transcription, Genetic Transfection cancer cell chromatin immunoprecipitation |
| Content Type | Text |
| Resource Type | Article |
