Reference : The 6-Kilobase C-Erbb2 Promoter Contains Positive and Negative Regulatory Elements Fu...
Scientific journals : Article
Human health sciences : Oncology
Life sciences : Biochemistry, biophysics & molecular biology
The 6-Kilobase C-Erbb2 Promoter Contains Positive and Negative Regulatory Elements Functional in Human Mammary Cell Lines
Grooteclaes, Madeleine mailto [> > > >]
Pasleau, Françoise mailto [Université de Liège - ULg > CARE "Le Réseau des bibliothèques de l'ULg" > Bibliothèque des Sciences de la vie >]
Dijkmans, Huguette [> > > >]
Berzi, Paulette mailto [Université de Liège - ULg > Services administratifs généraux > R&D : Gestion stratégique >]
Albert, Adelin mailto [Université de Liège - ULg > Département des sciences de la santé publique > Informatique médicale et biostatistique >]
Winkler-Gol, Rose mailto [> > > >]
Cancer Research
Yes (verified by ORBi)
[en] A 6-kilobase fragment extending at the 5'-end of the c-erbB2 protooncogene was isolated from a normal human lymphocyte genomic DNA library. The full-length fragment and five subfragments with identical 3'-ends were obtained by progressive unidirectional deletion from the 5'-end and were cloned in front of the luciferase reporter gene. The hybrid genes were analyzed for transcriptional activity in human mammary cell lines synthesizing low (HBL-100 and T-47D), moderate (MDA-MB-453), or high (BT-474) amounts of the c-erbB2 mRNA and were also analyzed in HeLa cells. Gene-specific expression was observed, indicating the presence of multiple cis-acting sequences in the c-erbB2 promoter. A major negative element is located in the -2- to -4-kilobase region. It is flanked on both sides by positive elements that display enhanced transcriptional activity in the BT-474 tumor cells only. While predominant in the low-expressing cells, the effect of the repressor appears to be overcome by the distal transactivator in the high-expressing BT-474 cells, resulting in a 15 to 50 times increase in luciferase activity relative to the HBL-100 and T-47D cells, respectively. Cell-specific expression relies on the trans-acting factors present in the different cell lines. The formation of cell-specific protein-DNA complexes was demonstrated by gel retardation assay.
Researchers ; Professionals

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