Expression of the WT1 Wilms' tumor gene by normal and malignant human melanocytes

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Abstract

We report expression of the wt I (Wilms' tumor) gene by cultured human melanoma cells. Using RNA polymerase chain reaction analysis, wt I transcripts were detected in 7 of 9 melanoma cell lines but not in 5 normal melanocyte strains. In Northern blot analysis, steady-state wt I mRNA levels were found in 2 of 4 melanoma lines but not in normal melanocytes. Sequence analysis of the wt I cDNA expressed by melanoma cell line WM 902-B revealed the presence of 4 previously published splice variants but no evidence for mutations in the coding region. Previous work has shown that WT I modulates transcription after binding to the early growth response (EGR)-I sites present in the platelet-derived growth factor (PDGF)-A chain promoter; the PDGF-A chain gene is known to be expressed by various melanoma cell lines. Based on these findings, we studied the relationship of wt I and PDGF-A chain gene expression in melanoma cell lines. Co-expression of the wt I and the PDGF-A chain genes was observed in 2 melanoma cell lines with mutated p53 but not in 2 melanoma cell lines with wild-type p53; this result is consistent with a previous report showing that, in the context of absent or mutated p53, WTI acts as a transcriptional activator, whereas in the presence of wild-type p53 it acts as a repressor.

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