Up-regulation of MET expression by α-melanocyte-stimulating hormone and MITF allows hepatocyte growth factor to protect melanocytes and melanoma cells from apoptosis

Laurent Beuret, Enrica Flori, Christophe Denoyelle, Karine Bille, Roser Busca, Mauro Picardo, Corine Bertolotto, Robert Ballotti

Research output: Contribution to journalArticle

Abstract

The MET proto-oncogene encodes for the hepatocyte growth factor (HGF) receptor, a plasma membrane tyrosine kinase that is involved in melanocyte growth and melanoma development. In mouse melanoma cells, Met expression is increased by αMSH via the activation of the cAMP pathway. However, the mechanism by which cAMP regulates MET and the biological consequences of this increase were not known. In the present report, we show that αMSH regulates MET expression in both human melanocytes and mouse melanoma cells through a transcriptional mechanism that requires MITF. Furthermore, the adenovirus driven expression of MITF is sufficient to increase MET in melanoma cells. Functional analysis of the MET promoter allows us to identify an E-box motif conserved in both human and mouse promoter that mediates the effect of MITF. Interestingly, up-regulation of MET expression by cAMP leads to an exacerbated HGF signaling and allows HGF to protect melanocytes and melanoma cells from apoptosis. Thus, physiological stimuli or pathological events that would induce MITF expression may lead to increased MET expression thereby favoring melanoma survival. These observations strengthen the roles of MITF and MET in melanoma development.

Original languageEnglish
Pages (from-to)14140-14147
Number of pages8
JournalJournal of Biological Chemistry
Volume282
Issue number19
DOIs
Publication statusPublished - May 11 2007

Fingerprint

Melanocyte-Stimulating Hormones
Hepatocyte Growth Factor
Melanocytes
Melanoma
Up-Regulation
E-Box Elements
Proto-Oncogene Proteins c-met
Apoptosis
Functional analysis
Cell membranes
Protein-Tyrosine Kinases
Chemical activation
Proto-Oncogenes
Growth and Development
Adenoviridae
Cell Membrane
Survival

ASJC Scopus subject areas

  • Biochemistry

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Up-regulation of MET expression by α-melanocyte-stimulating hormone and MITF allows hepatocyte growth factor to protect melanocytes and melanoma cells from apoptosis. / Beuret, Laurent; Flori, Enrica; Denoyelle, Christophe; Bille, Karine; Busca, Roser; Picardo, Mauro; Bertolotto, Corine; Ballotti, Robert.

In: Journal of Biological Chemistry, Vol. 282, No. 19, 11.05.2007, p. 14140-14147.

Research output: Contribution to journalArticle

Beuret, Laurent ; Flori, Enrica ; Denoyelle, Christophe ; Bille, Karine ; Busca, Roser ; Picardo, Mauro ; Bertolotto, Corine ; Ballotti, Robert. / Up-regulation of MET expression by α-melanocyte-stimulating hormone and MITF allows hepatocyte growth factor to protect melanocytes and melanoma cells from apoptosis. In: Journal of Biological Chemistry. 2007 ; Vol. 282, No. 19. pp. 14140-14147.
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AU - Bille, Karine

AU - Busca, Roser

AU - Picardo, Mauro

AU - Bertolotto, Corine

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AB - The MET proto-oncogene encodes for the hepatocyte growth factor (HGF) receptor, a plasma membrane tyrosine kinase that is involved in melanocyte growth and melanoma development. In mouse melanoma cells, Met expression is increased by αMSH via the activation of the cAMP pathway. However, the mechanism by which cAMP regulates MET and the biological consequences of this increase were not known. In the present report, we show that αMSH regulates MET expression in both human melanocytes and mouse melanoma cells through a transcriptional mechanism that requires MITF. Furthermore, the adenovirus driven expression of MITF is sufficient to increase MET in melanoma cells. Functional analysis of the MET promoter allows us to identify an E-box motif conserved in both human and mouse promoter that mediates the effect of MITF. Interestingly, up-regulation of MET expression by cAMP leads to an exacerbated HGF signaling and allows HGF to protect melanocytes and melanoma cells from apoptosis. Thus, physiological stimuli or pathological events that would induce MITF expression may lead to increased MET expression thereby favoring melanoma survival. These observations strengthen the roles of MITF and MET in melanoma development.

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