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Carcinogenesis Advance Access published online on June 17, 2004
Carcinogenesis, doi:10.1093/carcin/bgh215
© 2004 by Oxford University Press
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Received February 2, 2004
Revised May 30, 2004
Accepted June 10, 2004

CANCER BIOLOGY

Identification of a functional variant of estrogen receptor beta in an African population

Chunyan Zhao 1, Li Xu 1, Michio Otsuki 1, Gudrun Toresson 1, Konrad Koehler 2, Qiang Pan-Hammarström 1, Lennart Hammarström 1, Stefan Nilsson 2, Jan-Åke Gustafsson 1, Karin Dahlman-Wright 1*

1 Karolinska Institute, Department of Biosciences at Novum, S-141 57 Huddinge, Sweden
2 KaroBio AB, Novum, S-141 57 Huddinge, Sweden

* To whom correspondence should be addressed. E-mail: kada{at}cbt.ki.se.


  Abstract

In this study, we identified five novel polymorphisms in the estrogen receptor beta (ER{beta}) gene in an African population. Interestingly, two of these variants are expected to change the amino acid sequence of the ER{beta} protein. These changes correspond to an Isoleucine to Valine substitution at amino acid position 3 (I3V) and a Valine to Glycine substitution at position 320 (V320G), respectively. The functional consequences of these amino acid substitutions were determined in different in vitro assays. The I3V mutation displayed no differences with regard to transcriptional activity in a reporter assay, as compared to the wild type receptor. The V320G mutation, however, showed significantly decreased maximal transcriptional activity in a reporter assay, though its binding affinity for 17{beta}-estradiol was not affected. A pull-down assay indicated that the interaction of full-length TIF2 with hER{beta}V320G was weaker than with hER{beta}wt. Moreover, surface plasmon resonance (SPR) analysis revealed reduced interaction of the V320G ER{beta} variant with the NR box I and II modules of TIF2. To our knowledge, this represents the first identification of a functional polymorphism in the ER{beta} gene. This novel polymorphism provides a tool for human genetic studies of diseases in the African population.

Keywords: estrogen receptor beta, polymorphism, ligand, TIF2, transactivation
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