The 6 kb c-erbB2 promoter contains positive and negative regulatory elements functional in human mammary cell lines.

Conference (1994, September)

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

in Cancer Research (1994), 54(15), 4193-9

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 ... [more ▼]

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. [less ▲]

La région régulatrice du gène c-erbB2 contient des éléments cis-activateurs et inhibiteurs actifs dans des lignées de cellules épithéliales mammaires humaines.

Conference (1994, June)

Molecular mechanisms of deregulated c-erbB2 gene expression in human breast cancers.

Conference (1994, March 31)

La région régulatrice du gène c-erbB2 contient des éléments cis-activateurs et inhibiteurs actifs dans des lignées de cellules épithéliales mammaires humaines.

in Bucabs (1994), (81), 538

Molecular alterations in breast cancers : deregulation of c-erbB2 gene expression.

Conference (1993, September)

Expression of the C-Erbb2 Gene in the Bt474 Human Mammary Tumor Cell Line: Measurement of C-Erbb2 Mrna Half-Life

in Oncogene (1993), 8(4), 849-54

BT474 and SK-BR-3 mammary adenocarcinoma cells contain eight copies of the c-erbB2 gene but overexpress the mRNA 80 times over the levels measured in normal breast or in the HBL-100 cell line. Using ... [more ▼]

BT474 and SK-BR-3 mammary adenocarcinoma cells contain eight copies of the c-erbB2 gene but overexpress the mRNA 80 times over the levels measured in normal breast or in the HBL-100 cell line. Using Northern blot analysis and molecular titration based on RNAase protection assay, the decrease in the c-erbB2 mRNA level was monitored in BT474 cells treated with actinomycin D from 1 up to 24 h. The c-erbB2 degradation rate during the first 12 h corresponds to a calculated c-erbB2 mRNA half-life of approximately 7 h. Forty percent of the mRNA present in the cells before treatment remains undegraded after transcription has been blocked for 24 h. Pretreatment with cycloheximide results in complete mRNA degradation in 24 h, suggesting that labile proteins stabilize part of the c-erbB2 mRNA population. Comparison with the c-erbB2 mRNA turnover in HBL-100 'normal' cells indicated that the accumulation of the c-erbB2 gene product in the tumor cells is not the result of stabilization of the messenger. Rather, it is correlated with an increased rate of c-erbB2 mRNA transcription as indicated by run-on transcription assays. Both BT474 and SK-BR-3 tumor cell lines were found to synthesize 20-40 times more c-erbB2 mRNA than HBL-100 cells. [less ▲]

Etude de l'expression de l'oncogène c-erbB2 dans les cellules épithéliales mammaires humaines "normales" HBL-100 et tumorales BT-474.

Conference (1992, November 24)

Tissue-specific expression of c-erbB2 LUC reporter genes transiently transfected in cervix adnocarcinoma HeLa cells or in "normal" HBL-100 or tumor BT474 mammary epithelial cell lines.

Poster (1992, September)

Expression transitoire du promoteur c-erbB2 dans les cellules épithéliales mammaires normales et tumorales en culture.

Conference (1992, February)