Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia.

Pollock, Pamela M; Cohen-Solal, Karine; Sood, Raman; Namkoong, Jin; Martino, Jeffrey J; Koganti, Aruna; Zhu, Hua; Robbins, Christiane; Makalowska, Izabela; Shin, Seung-Shick; Marin, Yari; Roberts, Kathleen G; Yudt, Laura M; Chen, Amy; Cheng, Jun; Incao, Arturo; Pinkett, Heather W; Graham, Christopher L; Dunn, Karen; Crespo-Carbone, Steven M; Mackason, Kerine R; Ryan, Kevin B; Sinsimer, Daniel; Goydos, James; Reuhl, Kenneth R; Eckhaus, Michael; Meltzer, Paul S; Pavan, William J; Trent, Jeffrey M; Chen, Suzie

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Updated in 8/12/2020 12:04:31 PM

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(Journal Article)

Nature genetics 34 (1): 108-12 (2003)

Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia.

Pamela M Pollock , Karine Cohen-Solal , Raman Sood , Jin Namkoong , Jeffrey J Martino , Aruna Koganti , Hua Zhu , Christiane Robbins , Izabela Makalowska , Seung-Shick Shin , Yari Marin , Kathleen G Roberts , Laura M Yudt , Amy Chen , Jun Cheng , Arturo Incao , Heather W Pinkett , Christopher L Graham , Karen Dunn , Steven M Crespo-Carbone , Kerine R Mackason , Kevin B Ryan , Daniel Sinsimer , James Goydos , Kenneth R Reuhl , Michael Eckhaus , Paul S Meltzer , William J Pavan , Jeffrey M Trent , Suzie Chen

ABSTRACT
To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.

DOI: 10.1038/ng1148

ISSN: 1061-4036

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Position:	Professor
About me:	James Goydos, MD is widely recognized as an expert in melanoma research & surgical oncology. In his over 20 years of experience as a surgeon, he has conducted research that has translated into patient care, clinical trials, & cutting-edge treatment. His research and clinical trials have recorded growth arrest in melanoma cells, transforming the area of cancer genomics. Goydos has decades of experience as a Professor of Surgery and researcher at UMDNJ Robert Wood Johnson Medical School. He is an advocate for patient privacy and is recognized for leadership in patient care by the Cancer Institute of New Jersey and MRF. By 2020, his work in melanoma & innovative trials have led him to record numerous awards by Castle Connolly. He has helped individuals to better understand the mechanics of melanoma, the invasion of the dermis, and to see that it is not always a death sentence.
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