Overexpression of the Progestagen-Associated Endometrial Protein Gene Is Associated With Microphthalmia-Associated Transcription Factor in Human Melanoma

Background: We recently reported that the progestagen-associated endometrial protein (PAEP) gene is overexpressed and promotes tumor proliferation and metastasis in human melanoma. Methods: To identify the molecules that regulate its expression and oncogenic properties, we analyzed the gene microarray profiling of melanoma samples of serial clinical stage. Results: We found that the expression profile of the PAEP gene parallels that of microphthalmia-associated transcription factor (MITF, r = 0.86), a master regulator of melanocyte development and melanoma progression. This parallelism was further confirmed with semiquantitative reverse transcriptase polymerase chain reaction analysis of melanoma-derived daughter cells. Transfection of melanoma cells with MITF small interfering RNA (siRNA) specifically diminishes PAEP gene expression, whereas PAEP siRNA transfection has no effect on MITF. Furthermore, knockdown of either the MITF or PAEP gene reveals a significant inhibition of tumor cell migration. Conclusions: Our data indicate that PAEP expression is regulated in part by MITF and may thus play a role in MITF-mediated cell migration in human melanoma.