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 t ransgenes co-operate with the activated c-erbB-2 oncogene, neu, to for m metastatic mammary tumors, Elevated levels of S100A4 (p9Ka) in cultu red benign rat or mouse mammary epithelial cells are associated with t he induction of metastatic capability, A cis-acting sequence related t o the consensus recognition sequence of GC-factor, 1,300 base pairs up stream 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 l ine, but not in highly expressing rat mammary epithelial cell lines, T here is an inverse relationship between the level of S100A4 (p9Ka) mRN A 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.