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.