Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation.
Previously, we reported a transgenic mouse line, TG-3, that develops spontaneous melanoma with 100% penetrance. We demonstrated that ectopic expression of Grm1 in melanocytes was sufficient to induce melanoma in vivo. In this present study, the transforming properties of Grm1 in two cultured immortalized melanocytes were investigated. We showed that, in contrast to parental melanocytes, these Grm1-clones have lost their requirement of TPA supplement for proliferation and have acquired the ability to form colonies in semi-solid medium. Xenografts of these cells formed robust tumors in both immunodeficient nude and syngeneic mice with a short latency (3-5 days). The malignancy of these cells was demonstrated by angiogenesis and invasion to the muscle and the intestine. The requirement of Grm1 expression for the maintenance of transformation was demonstrated by an inducible siRNA system. Induction of expression of siRNA for Grm1 reduced the number of proliferating/viable cells in vitro and suppressed in vivo xenografted tumor growth in comparison with control. Taken together, these results showed that expression of exogeneously introduced Grm1 is sufficient to induce full transformation of immortalized melanocytes.
Shin
Seung-Shick
SS
Department of Chemical Biology, Ernest Mario School of Pharmacy, Susan Lehman Cullman Laboratory for Cancer Research, Rutgers University, Piscataway, NJ, USA.
Namkoong
Jin
J
Wall
Brian A
BA
Gleason
Ryan
R
Lee
Hwa Jin
HJ
Chen
Suzie
S
D000818:Animals; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008544:Melanocytes / Q000187:drug effects / Q000502:physiology*; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009857:Oncogenes / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D023041:Xenograft Model Antitumor Assays
D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1