The melanocyte-specific isoform of the microphthalmia transcription factor affects the phenotype of human melanoma.
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.
Selzer
Edgar
E
Department of Radiotherapy and Radiobiology, University Hospital Vienna, 1090 Vienna, Austria. Edgar.Selzer@AKH-Wien.ac.at
Wacheck
Volker
V
Lucas
Trevor
T
Heere-Ress
Elisabeth
E
Wu
Min
M
Weilbaecher
Katherine N
KN
Schlegel
Werner
W
Valent
Peter
P
Wrba
Fritz
F
Pehamberger
Hubert
H
Fisher
David
D
Jansen
Burkhard
B
D000818:Animals; D002461:Cell Line, Transformed; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D008544:Melanocytes / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D051739:Microphthalmia-Associated Transcription Factor; D020033:Protein Isoforms; D014157:Transcription Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; C497235:Mitf protein, mouse; D020033:Protein Isoforms; D014157:Transcription Factors