Transcriptional enhancement of the human gene encoding for a melanoma-associated antigen (ME491) in association with malignant transformation.

A cloned DNA fragment (lambda R31) containing the human gene for melanoma-associated ME491 antigen was transfected into mouse fibroblast cell lines and the antigen expression was studied. Our preliminary observation of higher expression of the antigen in more malignant Ltk- cells and weaker expression in less malignant NIH3T3 cells tempted us to investigate the antigen expression in Harvey(H)-ras-transformed NIH3T3 cells. It was observed that malignant transformation of the lambda R31-transfected NIH3T3 cells by H-ras oncogene enhanced the antigen expression to some extent. Northern blot analysis suggested that the enhancement occurred at the transcriptional level. Nucleotide sequence analysis of the 5'-regulatory region of the ME491 antigen gene in lambda R31 identified a number of consensus sequence motifs for binding of transcription factors such as Sp1, AP-2 and polyomavirus enhancer binding proteins 2 and 3. A consensus sequence motif for binding of AP-1, known as a ras-responsive element, was not found in that region. The significance and possible involvement of the transcription factors in the enhancement of ME491 antigen expression are discussed.