PMID- 8426746 OWN - NLM STAT- MEDLINE DCOM- 19930226 LR - 20220330 IS - 0950-9232 (Print) IS - 0950-9232 (Linking) VI - 8 IP - 2 DP - 1993 Feb TI - Regulatory mechanism of 92 kDa type IV collagenase gene expression which is associated with invasiveness of tumor cells. PG - 395-405 AB - 92-kDa Type IV collagenase, a member of matrix metalloproteinases, is believed to play a critical role in physiological tissue-remodeling processes and also in many pathological conditions such as tumor invasion. We analyzed the 5'-flanking sequence of the 92 kDa type IV collagenase gene that controls the expression of the gene by ligating it to the chloramphenicol acetyltransferase gene. Deletion and mutation analysis revealed that three motifs, homologous to the binding sites for AP-1, NF-kappa B, and Sp-1 proteins, contributed positively to induction by 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and tumor necrosis factor alpha (TNF alpha). The AP-1 site was indispensable but not sufficient for the induction and required synergistic cooperation with either the kappa B or the Sp-1 site. In OST cells, a nuclear factor which bound to Sp-1 was constitutively expressed, and those bound to AP-1 and kappa B elements were rapidly induced by TNF alpha treatment. Comparison of the findings with those for the promoters of other TPA-inducible matrix metalloproteinases, interstitial collagenase and stromelysin 1, revealed that the signal to the AP-1 sites is common for the TPA-inducibility of the genes but that the signals to the kappa B or Sp-1 sites, which are not present in interstitial collagenase and stromelysin 1 promoters, are the unique determinant for the inducibility of the 92 kDa type IV collagenase gene. FAU - Sato, H AU - Sato H AD - Department of Molecular Virology and Oncology, Kanazawa University, Ishikawa, Japan. FAU - Seiki, M AU - Seiki M LA - eng SI - GENBANK/D10051 PT - Journal Article PL - England TA - Oncogene JT - Oncogene JID - 8711562 RN - 0 (Proto-Oncogene Proteins c-jun) RN - 0 (Tumor Necrosis Factor-alpha) RN - 9007-49-2 (DNA) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.35 (Matrix Metalloproteinase 9) RN - NI40JAQ945 (Tetradecanoylphorbol Acetate) SB - IM MH - Base Sequence MH - Binding Sites MH - Collagenases/*genetics MH - DNA/metabolism MH - *Gene Expression Regulation, Enzymologic MH - Humans MH - Matrix Metalloproteinase 9 MH - Molecular Sequence Data MH - Neoplasm Invasiveness/*genetics MH - Promoter Regions, Genetic MH - Proto-Oncogene Proteins c-jun/pharmacology MH - TATA Box MH - Tetradecanoylphorbol Acetate/pharmacology MH - Transcription, Genetic MH - Transcriptional Activation MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 1993/02/01 00:00 MHDA- 1993/02/01 00:01 CRDT- 1993/02/01 00:00 PHST- 1993/02/01 00:00 [pubmed] PHST- 1993/02/01 00:01 [medline] PHST- 1993/02/01 00:00 [entrez] PST - ppublish SO - Oncogene. 1993 Feb;8(2):395-405.