The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma

• Published in: Cancer research (Chicago, Ill.) Ill.), 2002-04, Vol.62 (7), p.2098-2103
• Main Authors: SELZER, Edgar, WACHECK, Volker, FISHER, David, JANSEN, Burkhard, LUCAS, Trevor, HEERE-RESS, Elisabeth, MIN WU, WEILBAECHER, Katherine N, SCHLEGEL, Werner, VALENT, Peter, WRBA, Fritz, PEHAMBERGER, Hubert
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Line, Transformed; Dermatology; DNA, Complementary - genetics; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; Humans; Mast Cells - cytology; Mast Cells - metabolism; Mast Cells - physiology; Medical sciences; Melanocytes - cytology; Melanocytes - metabolism; Melanocytes - physiology; Melanoma - genetics; Melanoma - metabolism; Melanoma - pathology; Mice; Mice, SCID; Microphthalmia-Associated Transcription Factor; Protein Isoforms; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumors of the skin and soft tissue. Premalignant lesions
• ISSN: 0008-5472; 1538-7445

The microphthalmia transcription factor MITF plays a pivotal role in the development and differentiation of melanocytes. The purpose of this work was to investigate the expression and function of the melanocyte-specific isoform MITF-M in human melanoma. We found that MITF-M is repressed in 8 of 14 established melanoma cell lines tested. Transfection of MITF-M into a melanoma cell line (518A2) lacking the M-isoform and into a permanent cell line established from normal melanocytes (NMel-II) resulted in slower tumor growth in a severe combined immunodeficient-mouse xenotransplantation model. The growth difference between vector control-transfected tumors derived from the NMel-II cell line (mean tumor weight +/- SD, 3.2 g +/- 1.13) and MITF-M (+) transfectants (mean tumor weight +/- SD, 1.1 g +/- 0.49) was significant (P = 0.018). The mean tumor weight of control-transfected 518A2 tumors was 0.99 g +/- 0.22 and of MITF-M (+) transfectants, 0.69 g +/- 0.32. The difference in growth between 518A2 controls and the MITF-M (+) transfectants was clear, however it did not reach statistical significance (P = 0.08). In addition to the growth-inhibitory effects, MITF-M expression led to a change in the histopathological appearance of tumors from epitheloid toward a spindle-cell type in vivo. These results indicate a role for the MITF-M isoform in the in vivo growth control and the phenotype of human melanoma. In conclusion, MITF-M may qualify as a marker capable of identifying subgroups of melanoma patients with different tumor biology and prognosis.