A novel role of sodium butyrate in the regulation of cancer-associated aromatase promoters I.3 and II by disrupting a transcriptional complex in breast adipose fibroblasts
Deb, S; Zhou, J; Amin, SA; Imir, AG; Yilmaz, MB; Lin, Z; Bulun, SE
HERO ID
1455702
Reference Type
Journal Article
Subtype
Erratum
Year
2006
Language
English
PMID
| HERO ID | 1455702 |
|---|---|
| Material Type | Erratum |
| In Press | No |
| Year | 2006 |
| Title | A novel role of sodium butyrate in the regulation of cancer-associated aromatase promoters I.3 and II by disrupting a transcriptional complex in breast adipose fibroblasts |
| Authors | Deb, S; Zhou, J; Amin, SA; Imir, AG; Yilmaz, MB; Lin, Z; Bulun, SE |
| Journal | Journal of Biological Chemistry |
| Volume | 281 |
| Issue | 5 |
| Page Numbers | 2585-2597 |
| Abstract | The aromatase gene encodes the key enzyme for estrogen formation. Aromatase enzyme inhibitors eliminate total body estrogen production and are highly effective therapeutics for postmenopausal breast cancer. A distal promoter (I.4) regulates low levels of aromatase expression in tumor-free breast adipose tissue. Two proximal promoters (I.3/II) strikingly induce in vivo aromatase expression in breast fibroblasts surrounding malignant cells. Treatment of breast fibroblasts with medium conditioned with malignant breast epithelial cells (MCM) or a surrogate hormonal mixture (dibutyryl (Bt2)cAMP plus phorbol diacetate (PDA)) induces promoters I.3/II. The mechanism of promoter-selective expression, however, is not clear. Here we reported that sodium butyrate profoundly decreased MCM- or Bt2cAMP + PDA-induced promoter I.3/II-specific aromatase mRNA. MCM, Bt2cAMP + PDA, or sodium butyrate regulated aromatase mRNA or activity only via promoters I.3/II but not promoters I.1 or I.4 in breast, ovarian, placental, and hepatic cells. Mechanistically, recruitment of phosphorylated ATF-2 by a CRE (-211/-199, promoter I.3/II) conferred inductions by MCM or Bt2cAMP + PDA. Chromatin immunoprecipitation-PCR and immunoprecipitation-immunoblotting assays indicated that MCM or Bt2cAMP + PDA stabilized a complex composed of phosphorylated ATF-2, C/EBPbeta, and cAMP-response element-binding protein (CREB)-binding protein in the common regulatory region of promoters I.3/II. Overall, histone acetylation patterns of promoters I.3/II did not correlate with sodium butyrate-dependent silencing of promoters I.3/II. Sodium butyrate, however, consistently disrupted the activating complex composed of phosphorylated ATF-2, C/EBPbeta, and CREB-binding protein. This was mediated, in part, by decreased ATF-2 phosphorylation. Together, these findings represent a novel mechanism of sodium butyrate action and provide evidence that aromatase activity can be ablated in a signaling pathway- and cell-specific fashion. |
| Doi | 10.1074/jbc.M508498200 |
| Pmid | 16303757 |
| Wosid | WOS:000234931800022 |
| Url | http://www.jbc.org/content/281/14/9832.full |
| Is Certified Translation | No |
| Dupe Override | No |
| Comments | Source: Web of Science WOS:000234931800022 |
| Is Public | Yes |
| Language Text | English |
| Relationship(s) |
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