A new cis element is involved in the HER2 gene overexpression in human breast cancer cells.
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 Mr 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.
Grooteclaes
M
M
Department of Pathology, University of Liège, Belgium.
Vernimmen
D
D
Plaza
S
S
Pasleau
F
F
Hodzic
D
D
Winkler-Gol
R
R
D001483:Base Sequence; D001667:Binding, Competitive; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004586:Electrophoresis; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D009841:Oligonucleotides / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D066246:ErbB Receptors; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D050656:Transcription Factor AP-2; D014157:Transcription Factors; C000715470:MAS1 protein, human