TNF-alpha and IFN-gamma down-regulate the expression of the metastasis-associated bi-functional 37LRP/p40 gene and protein in transformed keratinocytes.
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-alpha and IFN-gamma. 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-gamma and TNF-alpha anticancerous action.
Clausse
N
N
Metastasis Research Laboratory, Sart Tilman, Liège, B-4000, Belgium.
van den Brûle
F
F
Delvenne
P
P
Jacobs
N
N
Franzen-Detrooz
E
E
Jackers
P
P
Castronovo
V
V
D002461:Cell Line, Transformed; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D009362:Neoplasm Metastasis; D011401:Promoter Regions, Genetic / Q000187:drug effects; D014176:Protein Biosynthesis; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D017474:Receptors, Laminin; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D011498:Protein Precursors; D012333:RNA, Messenger; D017474:Receptors, Laminin; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012269:Ribosomal Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D008156:Luciferases