Increased carcinogenic potential of myeloid tumor cells induced by aberrant TGF-β1-signaling and upregulation of cathepsin B

• DOI: 10.1515/bc.2007.072
• Publication Date: 2007-06-06T12:43:25Z
• Authors: Anita Reisenauer; Oliver Eickelberg; Aline Wille; Anke Heimburg; Annegret Reinhold; Bonnie F. Sloane; Tobias Welte; Frank Bühling
• Keywords: 0301 basic medicine; Apoptosis; Cathepsin B; Up-Regulation; Gene Expression Regulation, Neoplastic; Transforming Growth Factor beta1; 03 medical and health sciences; Cell Movement; Cell Line, Tumor; Humans; RNA; Promoter Regions, Genetic; Signal Transduction

Abstract The TGF-β signaling pathways are implicated in cancer. Cysteine cathepsins can contribute to the carcinogenic potential of tumor cells. aim this study was investigate regulation cysteine cathepsin expression by TGF-β1 and functional implications We found an upregulation B (CathB, 2- 5-fold) different myeloid cells (THP-1, MonoMac-1, MonoMac-6) after incubation with TGF-β1. No monocytes, there suppression CathB epithelial (A549). Increased activity led enhanced potential, which reflected increased migration invasion resistance inhibitor-induced apoptosis. Analysis showed no alterations TGF-β/BMP receptor or SMAD2/3 phosphorylation, influence MAP kinase pathways. However, a reduction SMAD1 detected. lack BMP action on cells, but not suggests defect Smad1/Smad5 pathway. located related TGF-β1-responsive element within first intron gene. In conclusion, pathway lead CathB, contributes