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Nuclear localization of EGF receptor and its potential new role as a transcription factor

Nature Cell Biology volume 3, pages 802–808 (2001)Cite this article

Abstract

Epidermal growth factor receptor (EGFR) has been detected in the nucleus in many tissues and cell lines. However, the potential functions of nuclear EGFR have largely been overlooked. Here we demonstrate that nuclear EGFR is strongly correlated with highly proliferating activities of tissues. When EGFR was fused to the GAL4 DNA-binding domain, we found that the carboxy terminus of EGFR contained a strong transactivation domain. Moreover, the receptor complex bound and activated AT-rich consensus-sequence-dependent transcription, including the consensus site in cyclin D1 promoter. By using chromatin immunoprecipitation assays, we further demonstrated that nuclear EGFR associated with promoter region of cyclin D1 in vivo. EGFR might therefore function as a transcription factor to activate genes required for highly proliferating activities.

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Figure 1: Immunohistochemical staining of different tissues for EGFR.
Figure 2: Detection of EGFR in the nuclear fractions of A431 and MDA-MB-468 cells.
Figure 3: Time-course study of EGFR nuclear localization.
Figure 4: Activation of gene expression by the C-terminus of EGFR (PRR domain).
Figure 5: AT-rich consensus sequences (ATRSs) identified by CASTing.
Figure 6: Activation of ATRS-specific reporter gene expression by EGF in EGFR-overexpressing cell lines.
Figure 7: ATRS-dependent activation of cyclin D1 promoter by EGF, and association of EGFR with cyclin D1 promoter in vivo.

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Acknowledgements

We thank You-Wei Chen for his assistance with the confocal microscopic analysis. The work was supported partly by NCI grants (to L.B. and M.-C.H.), an M.D. Anderson Faculty Achievement Award (to M.-C.H.) and a predoctoral fellowship from the DOD Breast Cancer Research Program (to S.-Y. L.). K.M. and Y.W. are supported by a DOD Breast Cancer Research Training Grant.

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  1. Shiaw-Yih Lin, Keishi Makino and Lilly Bourguignon: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular and Cellular Oncology, Breast Cancer Basic Research Program, The University of Texas M.D. Anderson Cancer Center, Houston, 77030, TX, USA

    Shiaw-Yih Lin, Keishi Makino, Weiya Xia, Angabin Matin, Yong Wen, Ka Yin Kwong & Mien-Chie Hung

  2. Endocrine Unit (111N), San Francisco VA Medical Center, UCSF, San Francisco, 94121, CA, USA

    Lilly Bourguignon

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Correspondence to Mien-Chie Hung.

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Lin, SY., Makino, K., Xia, W. et al. Nuclear localization of EGF receptor and its potential new role as a transcription factor. Nat Cell Biol 3, 802–808 (2001). https://doi.org/10.1038/ncb0901-802

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