The role of FOXO transcription factors in multiple myeloma
InstitutionsInstitut für Physiologische Chemie
Kliniken des Landkreises Heidenheim
Multiple Myeloma is a blood cancer deriving from malignant, monoclonal plasma cells. The transcription factor subclass “O” of the forkhead box (FOX) family of transcription factors 3 (FOXO3), which is mostly known as a tumor suppressor, showed an elevated expression level in Multiple Myeloma cells compared to plasma cells. Furthermore, Positive-regulatory-domain containing 1 (PRDM1), the master regulator of plasma cell differentiation, was shown in recent studies to be directly regulated by subclass “O” of the forkhead box (FOX) family of transcription factors 1 (FOXO1) in classical Hodgkin Lymphoma. Therefore, we investigated the role of FOXO transcription factors in the pathogenesis and maintenance of Multiple Myeloma. Using immunofluorescence staining we found that the subcellular distribution pattern of FOXO3 in Multiple Myeloma cell lines is very heterogenous and varies strongly among and within cell lines. Furthermore, we found that the used Multiple Myeloma cell lines were not sensitive to FOXO inhibition by the FOXO1 inhibitor AS1842856, indicating that FOXOs do not play a role in Multiple Myeloma maintenance. Moreover, FOXO down-regulation via the FOXO1 inhibitor AS1842856 did not lead to a significant change of PRDM1 protein expression and PRDM1, FOXO1 and p21 mRNA expression in Multiple Myeloma cell lines. Additionally, we found that FOXOs do not modulate the sensitivity to Bortezomib in Multiple Myeloma cell lines. Conclusively, in this present work, FOXO transcription factors could not be classified as tumor suppressors or proto-oncogenes in Multiple Myeloma cell lines. However, many insights have been gained, suggesting FOXO transcription factors as further important targets of investigation in the battle against Multiple Myeloma.
Subject HeadingsPlasmozytom [GND]
Multiple myeloma [MeSH]
Forkhead transcription factors [MeSH]
Positive regulatory domain I-binding factor 1 [MeSH]