- Paper Report
- Open Access
EGF receptor: new trick for an old dog?
- Douglas Yee1
© Biomed Central Ltd 2001
- Received: 24 October 2001
- Accepted: 26 October 2001
- Published: 1 December 2001
- EGF receptor, pathogenesis and cell biology, transcriptioin factors
Breast cancer biology is regulated by members of the epidermal growth factor receptor (EGFR) family. Traditionally, effects of these plasma membrane-associated tyrosine kinase receptors have been attributed to the activation of multiple diverse intracellular signaling pathways. However, nuclear localization of the EGFR has been documented although the function of these nuclear receptors is uncertain. In this study, the authors suggest that nuclear EGFR may function as a transcription factor.
Nuclear localization of the EGFR was documented. Transport of EGFR to the nucleus appeared to be ligand dependent, although, in EGFR-amplified cell lines, there appeared to be some constitutive nuclear EGFR. A transactivation domain was shown to be present in the C terminus of EGFR. Complexes of EGFR bound an AT-rich minimal consensus sequence (ATRS). Since the cyclin D1 promoter contains an ATRS, the authors used cyclin D1 promoter reporter constructs to show increased transcription after EGF treatment in MDA-468 breast cancer cells. Importantly, the authors showed that an EGFR complex could directly bind the cyclin D1 promoter. The authors concluded that EGFR can be transported into the nucleus after activation, and function as a transcription factor.
Immunohistochemistry, gene reporter constructs, cyclic amplification and selection of targets, chromatin immunoprecipitation, nuclear fractionation