A role for TGF-β in estrogen and retinoid mediated regulation of the nuclear receptor coactivator AIB1 in MCF-7 breast cancer cells
| Autor: | Anton Wellstein, Kristina J Lauritsen, Anna T. Riegel, Heinz-Joachim List, Ronald Reiter |
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| Rok vydání: | 2002 |
| Předmět: |
Cancer Research
Estrogen receptor Breast Neoplasms Tretinoin Retinoid X receptor Biology Nuclear Receptor Coactivator 3 Transforming Growth Factor beta Coactivator Tumor Cells Cultured Genetics Humans RNA Messenger skin and connective tissue diseases Fulvestrant Molecular Biology Estradiol Retinoid X receptor alpha Cell Cycle Gene Expression Regulation Neoplastic Nuclear receptor coactivator 3 Cancer research Nuclear receptor coactivator 2 Retinoid X receptor beta Estrogen receptor alpha Half-Life Transcription Factors |
| Zdroj: | Oncogene. 21:7147-7155 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1205943 |
| Popis: | AIB1 (amplified in breast cancer 1) is a nuclear receptor coactivator gene amplified and overexpressed in breast cancer. However, the mechanisms by which AIB1 is regulated are unclear. Here we show that 17beta-estradiol represses AIB1 mRNA and protein expression in MCF-7 human breast cancer cells primarily by suppressing AIB1 gene transcription. Estrogen levels present in fetal calf serum are sufficient to maintain AIB1 mRNA and protein at low basal levels, and this repression is reversed by the addition of antiestrogens or all-trans retinoic acid. Interestingly, cycloheximide inhibition experiments revealed that secondary protein synthesis was necessary to induce AIB1 expression by antiestrogens and retinoids. Experiments with TGF-beta and TGF-beta blocking antibodies demonstrated that this growth factor modulates AIB1 expression and showed that the antiestrogen and retinoid induction of AIB1 gene expression is mediated at least in part through TGF-beta. These data reveal a mechanism of estrogen-induced down-modulation of the overall hormone sensitivity of cells through feedback inhibition of coactivator gene expression. These data also suggest that antiestrogens can shift the sensitivity of cells to non-estrogenic proliferative signaling by increasing cellular levels of AIB1. This effect may play a role in breast cancer progression and resistance to drug treatment. |
| Databáze: | OpenAIRE |
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