Abstract
Late SV40 factor 3 (LSF), a transcription factor, contributes to human hepatocellular carcinoma (HCC). However, decreased expression level of LSF in skin melanoma compared to that in benign melanocytic tumors and nevi in mice and humans was found in this study. Anchorage-dependent and -independent growth of melanoma cells was suppressed by LSF overexpression through an increased percentage of G1 phase cells and an increased p21CIP1 expression level in vitro and in vivo. Anchorage-dependent growth in LSF-overexpressed melanoma cells was promoted by depletion of LSF in the LSF-overexpressed cells. Integrated results of our EMSA and chromatin immunoprecipitation assays showed binding of LSF within a 150-bp upstream region of the transcription start site of p21CIP1 in melanoma cells. Taken together, our results suggest potential roles of LSF as a growth regulator through control of the transcription of p21CIP1 in melanocytes and melanoma cells as well as a biomarker for nevus.
Highlights
50% of human melanomas have BRAF mutations [1]
Levels of Lsf transcript expression in normal murine tissues and other murine melanoma cells including B16 cells and Mel-ret cells were lower than those in benign melanocytic tumors and melanoma from RET-mice, whereas Lsf has been reported to be ubiquitously expressed in normal mouse tissues [10]
These results suggest that Lsf expression level in melanoma is lower than that in benign melanocytic tumors in mice
Summary
50% of human melanomas have BRAF mutations [1]. In the most common BRAF mutation (90% of cases), valine 600 is substituted by glutamic acid (V600E) [2]. We previously established Metallothionein-I/RFPRET transgenic mice (RET-mice) that spontaneously develop systemic skin melanosis, benign melanocytic tumors and melanoma metastasizing to distant organs [4, 5]. Both RET-mice and a Mel-ret murine melanoma cell line from the tumor of a RET-mouse [6] might be strong tools for analyzing the molecular mechanism of melanoma growth. We found opposite roles of LSF in melanoma compared to those previously reported in HCC and revealed a novel molecular mechanism of LSF in melanocytic cells in mice and humans
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