The 6-Kilobase C-Erbb2 Promoter Contains Positive and Negative Regulatory Elements Functional in Human Mammary Cell Lines

Grooteclaes, Madeleine; Pasleau, Françoise; Dijkmans, Huguette; Berzi, Paulette; Albert, Adelin; Winkler-Gol, Rose

Article (Scientific journals)

Grooteclaes, Madeleine; Pasleau, Françoise; Dijkmans, Huguette et al.

1994 • In Cancer Research, 54 (15), p. 4193-9

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Abstract :

[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.

Disciplines :

Oncology
Biochemistry, biophysics & molecular biology

Author, co-author :

Grooteclaes, Madeleine

Pasleau, Françoise ; Université de Liège - ULiège > CARE "Le Réseau des bibliothèques" > Bibliothèque des Sciences de la vie

Dijkmans, Huguette

Berzi, Paulette ; Université de Liège - ULiège > Services administratifs généraux > R&D : Gestion stratégique

Albert, Adelin ; Université de Liège - ULiège > Département des sciences de la santé publique > Informatique médicale et biostatistique

Winkler-Gol, Rose

Language :

English

Title :

The 6-Kilobase C-Erbb2 Promoter Contains Positive and Negative Regulatory Elements Functional in Human Mammary Cell Lines

Publication date :

01 August 1994

Journal title :

Cancer Research

ISSN :

0008-5472

eISSN :

1538-7445

Publisher :

American Association for Cancer Research, United States - Maryland

Volume :

Issue :

Pages :

4193-9

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 09 July 2009

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