Opposite regulation of estrogen receptor-α and its variant ER-α36 by the Wilms' tumor suppressor WT1

  • Authors: Lianguo Kang, Lei Wang, Zhao-Yi Wang
  • View Affiliations

  • Published online on: Friday, January 21, 2011
  • Pages: 337-341
  • DOI: 10.3892/ol.2011.250

Abstract

The genomic and non-genomic signaling pathways are well-known estrogen signaling pathways. The 66-kDa estrogen receptor-α (ER-α66) is a typical ligand-inducible transcription factor that mainly mediates genomic estrogen signaling. Recently, we identified and cloned a 36-kDa variant of ER-α66, known as ER-α36. This variant lacks intrinsic transcription activity and predominantly mediates non-genomic estrogen signaling. Thus, the expression of ER-α66 and ER-α36 should be dynamically regulated and carefully coordinated to maintain a balance between genomic and non-genomic estrogen signaling. However, the molecular mechanisms underlying this correlation remain poorly understood. The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger protein WT1 that functions as a dual transcription regulator to activate or suppress gene transcription. High levels of WT1 expression are associated with breast cancer malignancy. In the present study, high-passage ER-positive breast cancer MCF7 cells were found to express ER-α66 and WT1 at higher levels and ER-α36 at a very low level. Using the small hairpin RNA method, stable MCF7 cells were established that expressed knocked-down levels of WT1. The cells expressed a reduced level of ER-α66 but an increased level of ER-α36, suggesting that WT1 regulates the expression of ER-α66 and ER-α36 oppositely. Further co-transfection assays showed that all isoforms of WT1 directly activated the promoter activity of the ER-α66 gene while suppressing ER-α36 promoter activity. Our results therefore indicate that WT1 is a dual transcription factor that regulates the promoter activity of ER-α66 and ER-α36 oppositely, implicating WT1 as one of the coordinators that orchestrate genomic and non-genomic estrogen signaling.
Journal Cover

March 2011
Volume 2 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

2013 Impact Factor: 0.987
Ranked #149/202 Oncology
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APA
Kang, L., Wang, L., & Wang, Z. (2011). Opposite regulation of estrogen receptor-α and its variant ER-α36 by the Wilms' tumor suppressor WT1. Oncology Letters, 2(2), 337-341.
MLA
Kang, Wang, and Zhao-Yi Wang. "Opposite regulation of estrogen receptor-α and its variant ER-α36 by the Wilms' tumor suppressor WT1." Oncology Letters Oncology Letters 2.2 (2011): 337-341.
Chicago
Kang, Wang, and Zhao-Yi Wang. "Opposite regulation of estrogen receptor-α and its variant ER-α36 by the Wilms' tumor suppressor WT1." Oncology Letters Oncology Letters 2 no. 2 (2011): 337-341.