Metabotropic glutamate receptor subtype-1 is essential for in vivo growth of melanoma.
Ectopic expression of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse melanocytes induces melanoma formation. Although requirement of mGluR1 for development of melanoma in the initial stage has been demonstrated, its role in melanoma growth in vivo remains unclear. In this study, we developed novel transgenic mice that conditionally express mGluR1 in melanocytes, using a tetracycline regulatory system. Pigmented lesions on the ears and tails of the transgenic mice began to appear 29 weeks after activation of the mGluR1 transgene, and the transgenic mice produced melanomas at a frequency of 100% 52 weeks after transgene activation. Subsequent inactivation of the mGluR1 transgene in melanoma-bearing mice inhibited melanoma growth with reduction of immunoreactivity to phosphorylated ERK1/2, whereas mice with persistent expression of mGluR1 developed larger melanoma burdens. mGluR1 expression is thus required not only for melanoma development but also for melanoma growth in vivo. These findings suggest that growth of melanoma can be inhibited in vivo by eliminating only one of the multiple genetic anomalies involved in tumorigenesis.
Ohtani
Y
Y
Division of Molecular Genetics, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Kobe, Japan.
Harada
T
T
Funasaka
Y
Y
Nakao
K
K
Takahara
C
C
Abdel-Daim
M
M
Sakai
N
N
Saito
N
N
Nishigori
C
C
Aiba
A
A
D000818:Animals; D015153:Blotting, Western; D015870:Gene Expression; D011905:Genes, ras; D008546:Melanoma, Experimental / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; C482120:Braf protein, mouse; D048493:Proto-Oncogene Proteins B-raf