Transcriptional down-regulation of the metastasis-inducing S100A4 (p9Ka) in benign but not in malignant rat mammary epithelial cells by GC-factor.
The S100-related calcium-binding protein S100A4 (p9Ka) is expressed at a low level in rat mammary epithelial cells from normal mammary gland and benign mammary tumors. In transgenic mice, expressed rat S100A4 transgenes co-operate with the activated c-erbB-2 oncogene, neu, to form metastatic mammary tumors. Elevated levels of S100A4 (p9Ka) in cultured benign rat or mouse mammary epithelial cells are associated with the induction of metastatic capability. A cis-acting sequence related to the consensus recognition sequence of GC-factor, 1,300 base pairs upstream of the start site of transcription of the rat S100A4 gene, acts as a cis-acting inhibitor of transcription of the S100A4 (p9Ka) gene in a low S100A4 (p9Ka)-expressing benign rat mammary epithelial cell line, but not in highly expressing rat mammary epithelial cell lines. There is an inverse relationship between the level of S100A4 (p9Ka) mRNA and the level of GC-factor mRNA in a range of rat mammary cell lines. The results suggest a novel mechanism for regulating the expression of the mRNA encoding an S100 protein.
Chen
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Cancer and Polio Research Fund Laboratories, School of Biological Sciences, University of Liverpool, P. O. Box 147, Liverpool L69 7ZB, United Kingdom.
Davies
M P
MP
Rudland
P S
PS
Barraclough
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R
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015183:Restriction Mapping; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D017384:Sequence Deletion; D014158:Transcription, Genetic
D002135:Calcium-Binding Proteins; D012333:RNA, Messenger; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; C499412:S100a4 protein, rat