Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes.
Melanoma is the aberrant proliferation of melanocytes, the cells in the skin responsible for pigment (melanin) production. In its early stages, melanoma can be surgically removed with great success, however, advanced stages of melanoma have a high mortality rate due to the lack of responsiveness to currently available therapies. We have previously characterized a mouse melanoma model, TG-3, which has implicated the ectopic expression of metabotropic glutamate receptor 1 (Grm1, formerly mGluR1), in melanomagenesis and metastasis [Pollock et al., 2003. Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nat Genet. 34, 108-112.]. Here we report the characterization of several in vitro cell lines derived from independent mouse melanoma tumors. These cell lines show characteristic phenotypes of transformed melanocytes, and express Grm1, and Grm5 (another metabotropic glutamate receptor), as well as melanocyte-specific protein markers. To investigate the possible role of Grm5 in vivo during melanoma development in our mice, we have crossed Grm5 null mice with TG-3, generating a new line of transgenic mice, TGM. TGMs, which are homozygote knockouts for Grm5 and carry the TG transgene, develop tumors with onset, progression, and metastasis very similar to that described for TG-3. Taken together, these results indicate that Grm1 can act as an oncogene in melanocytes independently of Grm5 expression.
Marín
Yarí E
YE
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, 213, Ernest Mario School of Pharmacy, Rutgers University, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Namkoong
Jin
J
Shin
Seung-Shick
SS
Raines
Jason
J
Degenhardt
Kurt
K
White
Eileen
E
Chen
Suzie
S
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D004428:Ear Neoplasms / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism / Q000473:pathology; D008546:Melanoma, Experimental / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010088:Oxidoreductases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000172:deficiency / Q000378:metabolism* / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014407:Tumor Cells, Cultured
C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D013778:Tetrazolium Salts; D013844:Thiazoles; C104077:metabotropic glutamate receptor type 1; D010088:Oxidoreductases; C079621:Tyrp1 protein, mouse; C022616:thiazolyl blue