BRN2 in melanocytic cell development, differentiation, and transformation
MetadataShow full item record
POU domain transcription factors are critical regulators of many developmental processes, and can also be reactivated during malignancy. The BRN2 gene encoding the N-Oct-3 DNA binding activity is one such factor that is expressed in melanocytic cells. Cultured unpigmented epidermal human melanoblasts express high levels of BRN2 protein and DNA binding activity similar to metastatic melanoma cell lines, but this decreases after differentiation to a pigmented melanocyte phenotype. BRN2 expression can be increased by several melanocytic growth factors, some of which signal through the BRAF pathway, which is frequently mutated in melanoma. Ablation of BRN2 in melanoma cell lines produces a loss of melanocytic markers, decreased proliferation, and loss of tumorigenicity. Microarray analysis of these cell lines suggests that BRN2 resides upstream of other melanocytic transcription factors, such as SOX10, MITF, and SLUG, but below or in a separate hierarchy to PAX3. Because of the sensitivity of cells to POU protein expression levels in determination of cell fate, downregulation of BRN2 may act as a molecular switch in melanocytic cells to coordinate the onset of melanogenesis with differentiation, but which can be aberrantly reactivated in melanoma.
From Melanocytes to Melanoma: The Progression to Malignancy
Cell Development, Proliferation and Death