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A New cis Element Is Involved in the HER2 Gene Overexpression in Human Breast Cancer Cells¹

Laboratory of Molecular Oncology, Department of Pathology [M. G., D. V., D. H., R. W-G.] and Faculty of Medicine Library, University Hospital Center [F. P.], University of Liège, 4000 Liège, Belgium, and Laboratory of Regulation of Invasive Processes, Angiogenesis and Apoptosis, Institut Pasteur, 59019 Lille, France [S. P.]

The HER2 proto-oncogene product is overexpressed in 30% of breast cancers, and this correlates with poor prognosis. Increased levels of HER2 mRNA in breast cancer cell lines result from increased gene transcription. We report the identification of a new 17-bp-long cis sequence located between positions -506 and -489 from the transcription start site. This sequence is recognized by a trans-activating factor that we tentatively named HER2 transcription factor (HTF). This factor, involved in the increased transcription of the HER2 gene in the BT-474 mammary tumor cells, has a molecular weight of about M_r 50,000. HTF can also bind, but with a lower affinity, to a related cis sequence present in the epidermal growth factor receptor promoter. Interestingly, the HTF binding activity is high in nuclear extracts from several mammary tumor cells overexpressing the HER2 gene.

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