Suzie Chen
Professor

Mouse model of melanoma. regulation of cell signaling by G-protein-coupled receptor

The two areas of research in my laboratory are 1). a transgenic mouse model system for melanoma development. and 2). Regulation of cell signaling by G-protein-coupled-receptor:

Malignant melanoma. a very aggressive type of skin cancer. if detected and removed at an early stage. the overall 5-year survival rate is relatively high. However. if the lesions are not detected and removed at an early stage. metastasis may occur and spread to other parts of the body. which is associated with high mortality rate. Currently. malignant melanoma is largely refractory to conventional therapies.

A transgenic mouse line that displays melanoma phenotype spontaneously was developed in our lab. We showed and confirmed the aberrant expression of a G-protein-coupled-receptor (metabotropic glutamate receptor 1. Grm1) in melanocytes to be responsible for the generation of melanoma in our system. Expression of GRM1 has been detected in some human melanoma cell lines and biopsy samples. suggesting possible involvement of this receptor in some cases of human melanoma. Normally Grm1 is predominantly associated with excitatory synaptic neurotransmission in the mammalian central nervous system. The signaling cascades activated by the ligand. glutamate. are believed to be equally important in regulating the growth and differentiation of a wide variety of both neural and non-neural cells. We hypothesize that one of the consequences of deregulation of Grm1 expression in melanocytes is activation of pathways leading to increase in cell proliferation and/or decrease in apoptosis. resulting in cell transformation and tumor development. The long term goals of our lab are to identify and characterize the signaling pathway(s) utilized by Grm1 ectopically expressed in melanocytes. and downstream targets of the oncogenic effects exerted by activated Grm1 in our system and to use our model system to better understand this complex disease and apply our knowledge to development of more effective agents with fewer side effects for the prevention and treatment of cancer.

Selected Publications

Shin SS, Namkoong J, Wall BA, Gleason R, Lee HJ, Chen S. (2008) Oncogenic activities of metabotropic glutamate receptor 1 (Grm1) in melanocyte transformation. Pigment Cell Melanoma Res. 21(3):368-78.

Marín YE, Wall BA, Wang S, Namkoong J, Martino JJ, Suh J, Lee HJ, Rabson AB, Yang CS, Chen S, Ryu JH. (2007) Curcumin downregulates the constitutive activity of NF-kappaB and induces apoptosis in novel mouse melanoma cells. Melanoma Res. 17(5):274-83.

Namkoong J, Shin SS, Lee HJ, Marin YE, Wall BA, Goydos JS, Chen S. (2007) Metabotropic glutamate receptor 1 and glutamate signaling in human melanoma. Cancer Res. 67(5):2298-305.

Namkoong J. Martino JJ. Chen S. (2006) From existing therapies to novel targets: a current view on melanoma. Front Biosci. 11:2081-92.

Marin YE. Namkoong J. Cohen-Solal K. Shin SS. Martino JJ. Oka M. Chen S. metabotropic glutamate receptor 1 in melanoma cells activates ERK1/2 via PKCepsilon. Cell Signal. (2006) Stimulation of oncogenic 18(8):1279-86.

Hansson A. Marin YE. Suh J. Rabson AB. Chen S. Huberman E. Chang RL. Conney AH. Zheng X. (2005) Enhancement of TPA-induced growth inhibition and apoptosis in myeloid leukemia cells by BAY 11-7082. an NF-kappaB inhibitor. Int J Oncol. 27(4):941-8.

Marin YE. Namkoong J. Shin SS. Raines J. Degenhardt K. White E. Chen S. (2005) Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes. Neuropharmacology. 49 Suppl 1:70-9.

Marin. Y and Chen. S. (2004) Involvement of metabotropic glutamate receptor 1. a G-protein-coupled receptor. in melanoma development. J. Mol. Med. 82: 735-749.

Pollock. P.M.. Cohen-Solal. K.A.. Sood. R.. Namkoong. J.. Koganti. A.. Zhu. H.. Robbins. C.. Makalowska. I.. Martino. J.J.. Shin. S-S. Marin. Y.. Roberts. K.G.. Yudt. L.M.. Chen. A.. Cheng. J.. Incao. A.. Pinkett. H.W.. Graham. C.L.. Dunn. K.. Crespo-Carbone. S.M.. Mackason. K.R.. Ryan. K.B.. Sinsimer. D.. Goydos. J.. Reuhl. K.R.. Eckhaus. M.. Meltzer. P.S.. Pavan. W.J.. Trent. J.M. and Chen. S. (2003). Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia. Nature Genetics. 34: 108-112.

Sood. R.. Makalowska. I.. Galdzicki. M.. Hu. P.. Eddings. E.. Robbins. C.M.. Moses. T.. Namkoong. J.. Chen. S.. and Trent. J.M. (2003). Cloning and characterization of a novel gene SHPRH encoding a conserved putative protein with SNF2/helicase and PHD-finger domains from 6q24 region. Genomics 82:153-161.

Cohen-Solal. K.A.. Sood. R.. Marin. Y.. Crespo-Carbone. S.M.. Sinsimer. D.. Martino. J.J.. Robbins. C.. Makalowska. I.. Trent. J.M. and Chen. S.. (2003). Identification and characterization of mouse Rab32 by mRNA and protein expression analysis. Biochem. Biophys. Acta. 1651:68-15.

Cohen-Solal. K.A.. Crespo-Carbone. S.M.. Namkoong. J.. Mackason. K.R.. Roberts. K.G.. Reuhl. K.R. and Chen. S. (2002). Progressive appearance of pigmentation in amelanotic melanoma lesions. Pigment Cell Res. 15: 282-289.

Cohen-Solal. K.A.. Reuhl. K.R.. Ryan. K.B.. Roberts. K.G. and Chen. S. (2001). Development of cutaneous amelanotic melanoma in the absence of a functional tyrosinase. Pigment Cell Res.14: 466-474.