Identification of a minimal c-erbB-2 promoter region that mediates preferential expression of a linked foreign gene in human breast cancer cells.
The c-erbB-2 oncogene is frequently overexpressed in human breast cancer partly due to its elevated transcription level. The promoter regions of the c-erbB-2 gene could therefore activate the transcription of a linked foreign gene preferentially in breast cancer cells. Previous reports showed that the 533-bp (-495/+38, +1 corresponds to the transcription start site) or the 251-bp (-213/+38) genomic fragment included the cis-acting elements which stimulated the transcription of a fused gene in breast cancer cells. Our previous study also indicated that the 251-bp fragment could transcribe the reporter gene better than the 533-bp fragment and that the 124-bp (-86/+38) region did not support the transcription of a linked reporter gene. In this study, we precisely analyzed the promoter activity of the genomic region between -213/+38 and -86/+38 in breast cancer, non-breast cancer cells and fibroblasts, and found that deletion of 22-bp from the 251-bp fragment markedly decreased the transcriptional activation in breast cancer cells. Although the 22-bp deletion also decreased the promoter activity in non-breast cancer cells, the deletion did not influence the activity in fibroblasts. Since the promoter activity of shorter genomic fragments beyond the 22-bp deletion remained low in breast cancer cells, the -213/-191 region contains a cis-acting element(s) that is minimally required for the preferential expression in breast cancer cells.
Yu
Ling
L
Division of Pathology, Chiba Cancer Center Research Institute, Chiba 260-8717, Japan.
Kamo
Sakurako
S
Tagawa
Masatoshi
M
D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics*; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism; D017353:Gene Deletion; D008040:Genetic Linkage; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D008156:Luciferases; D018719:Erb-b2 Receptor Tyrosine Kinases