Investigation of the relationship between MITF and POU3F2 expression and the notion of a "genetic switch" underlying phenotype switching in melanoma.

e22081 Background: Clear understanding of the transition from non-invasive to an invasive phenotype in melanoma remains elusive. Microphthalmia-associated transcription factor (MITF), a central player in melanoma biology, controls many aspects of the melanocytic lineage. However, recently the POU domain transcription factor family member, POU3F2/BRN2, was shown to directly repress MITF expression, and conversely MITF was shown to repress POU3F2 via the increased expression of microRNA, miR-211. This raises the possibility of a “genetic switch” facilitated by the alternating expression levels of MITF or POU3F2in melanoma. Methods: To characterize whether a “genetic switch” may underlie phenotype switching in melanoma we used RNAi to investigate knockdown of POU3F2 versus MITFin metastatic and primary melanoma cell lines. The cell lines were classified into two groups; “high MITF expression” and “Low MITF expression” by QRT-PCR. The effect of MITF expression level on cell migration was investigated using scratch and Boyden chamber assays. Results: Inhibition of POU3F2 expression by RNAi reduced cell migration in