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ERK‐regulated differential expression of the Mitf 6a/b splicing isoforms in melanoma
Author(s) -
Primot Aline,
Mogha Ariane,
Corre Sébastien,
Roberts Karen,
Debbache Julien,
Adamski Henri,
Dreno Brigitte,
Khammari Amir,
Lesimple Thierry,
Mereau Agnes,
Goding Colin R,
Galibert MarieDominique
Publication year - 2010
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/j.1755-148x.2009.00652.x
Subject(s) - microphthalmia associated transcription factor , alternative splicing , gene isoform , melanoma , biology , cancer research , exon , irf4 , microbiology and biotechnology , genetics , gene , transcription factor
Summary The master regulator of the melanocyte lineage Mitf is intimately involved in development as well as melanoma, controlling cell survival, differentiation, proliferation and metastasis/migration. Consistent with its central role, Mitf expression and Mitf post‐translational modifications are tightly regulated. An additional potential level of regulation is afforded by differential splicing of Mitf exon‐6 leading to the generation of two isoforms that differ by the presence of six amino‐acids in the Mitf (+) isoform and which have differential effects on cell cycle progression. However, whether the ratio of the two isoforms is regulated and whether their expression correlates with melanoma progression is not known. Here, we show that the differential expression of the Mitf 6a/b isoforms is dependent on the MAPKinase signalling, being linked to the activation of MEK1‐ERK2, but not to N‐RAS/B‐RAF mutation status. In addition, quantification of Mitf 6a/b splicing forms in 86 melanoma samples revealed substantially increased levels of the Mitf ( − ) form in a subset of metastatic melanomas. The results suggest that differential expression of the Mitf 6a/b isoforms may represent an additional mechanism for regulating Mitf function and melanoma biology.