TNF-α and IFN-γ Down-Regulate the Expression of the Metastasis-Associated Bi-functional 37LRP/p40 Gene and Protein in Transformed Keratinocytes

• Published in: Biochemical and biophysical research communications Vol. 251; no. 2; pp. 564 - 569
• Main Authors: Clausse, Nathalie, van den Brûle, Frédéric, Delvenne, Philippe, Jacobs, Nathalie, Franzen-Detrooz, Elisabeth, Jackers, Pascale, Castronovo, Vincent
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 20.10.1998; Elsevier
• Subjects: 37 LRP/p40; 67LR; bi-functional; Cell Line, Transformed; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; HeLa Cells; Human health sciences; Humans; IFN-gamma; IFN-γ; Interferon-gamma - pharmacology; Keratinocytes - cytology; Keratinocytes - drug effects; Keratinocytes - metabolism; Luciferases - biosynthesis; Luciferases - genetics; metastasis-associated; Neoplasm Metastasis; Oncologie; Oncology; Promoter Regions, Genetic - drug effects; Protein Biosynthesis; Protein Precursors - biosynthesis; Protein Precursors - genetics; Receptors, Laminin; Recombinant Fusion Proteins - biosynthesis; Recombinant Proteins - pharmacology; Ribosomal Proteins - biosynthesis; Ribosomal Proteins - genetics; RNA, Messenger - metabolism; Sciences de la santé humaine; TNF-alpha; TNF-α; Transcription, Genetic; Transfection; Tumor Necrosis Factor-alpha - pharmacology; metastasis-associated; IFN-γ; bi-functional; 37 LRP/p40; TNF-α; 67LR
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1006/bbrc.1998.9431

The 37 LRP/p40 molecule is a bi-functional protein in which expression is increased in a large variety of cancers in association with their metastatic phenotype. Here we present the first data concerning the 37 LRP/p40 gene promoter activity and show that it is very active in a cervix carcinoma cell line. Interestingly, despite hallmarks of a housekeeping gene, we show that the 37 LRP/p40 gene promoter can be down-regulated by two potentially anticancerous cytokines, TNF-α and IFN-γ. In addition, the dual fate of the protein, i.e., being intracellularly involved in the cell translation machinery and incorporated into a 67-kDa cell surface protein functioning as a laminin receptor (67LR), is differentially affected by the treatment. Our data suggest multiple regulation levels in the control of the 67LR/37LRP/p40 molecule expression and uncover new clues for the understanding of both the control of expression of this metastasis-associated molecule and the IFN-γ and TNF-α anticancerous action.