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Mechanisms regulating c‐met overexpression in liver‐metastatic B16‐LS9 melanoma cells
Author(s) -
Elia Giuliano,
Ren Yuan,
Lorenzoni Patrizia,
Zarnegar Reza,
Burger Max M.,
Rusciano Dario
Publication year - 2001
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/1097-4644(20010601)81:3<477::aid-jcb1061>3.0.co;2-b
Subject(s) - hepatocyte growth factor , downregulation and upregulation , hepatocyte , biology , transcription factor , microbiology and biotechnology , receptor , cell culture , messenger rna , cancer research , gene , endocrinology , genetics , in vitro
Liver selected B16‐LS9 melanoma cells show a dramatic overexpression of the proto‐oncogene c‐met, the cellular receptor for hepatocyte growth factor/scatter factor. As a consequence, c‐met becomes constitutively active, and the cells become more responsive to hepatocyte growth factor stimulation. We have investigated the molecular mechanisms regulating c‐met expression in both the parental line B16‐F1, which has low expression levels, and the liver‐specific B16‐LS9, overexpressing c‐met. Overexpression is observed at the protein and mRNA levels, however without further evidence of gene amplification or rearrangement. c‐met promoter activity was higher in B16‐LS9 than B16‐F1 cells, and also a nuclear run‐off showed higher transcription levels in B16‐LS9 cells. Moreover, we found that c‐met mRNA had a longer half‐life in B16‐LS9 cells, thus indicating also the involvement of post‐transcriptional regulation mechanisms. Finally, we found evidence that autonomous activation of the melanocortin receptor‐1 (MCR‐1) is at least partially responsible for c‐met upregulation in B16‐LS9 cells, since treatment of the cells with a potent MSH antagonist (the agouti peptide) has strong down‐regulatory effects. J. Cell. Biochem. 81:477–487, 2001. © 2001 Wiley‐Liss, Inc.