 | Jairo Sierra Montclair State University BiologyMentor(s)Suzie Chen, Ph.D. Janet Wangari-Talbot Department of Chemical Biology Rutgers University |
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| Suppression of GRM1 expression by siRNA in an ecdysone-regulated system in a human melanoma cell line | ||
| Melanoma is a form of skin cancer that arises from the neoplastic transformation of the pigment producing cells of the epidermis, melanocytes. According to the 2009 American Cancer Society estimates, in the United States alone, ~ 68,000 individuals will be diagnosed with melanoma with ~ 8000 of these cases resulting in deaths. Current treatments for metastatic melanoma include chemotherapy, radiation, surgical resection as well as adjuvant immunotherapy. Major problems such as tumor recurrence and unpleasant side effects arising from these treatments require the need for new therapies. Previously our laboratory identified that the ectopic expression of GRM1 (metabotropic glutamate receptor I) in melanocytes was sufficient to induce melanoma in a transgenic mouse model (TG-3). Analysis of human biopsy samples as well as human melanoma cell lines showed that ~ 40% of the samples were positive for GRM1 expression. We hypothesize that reduction of GRM1 expression by either pharmacological or genetic mechanisms might be a way to reduce melanoma progression. For the genetic regulation of GRM1 expression, we are developing a siRNA system which is switched on by the presence of 20-OH ecdysone (ponasterone A) and turned off when the inducer is absent. Our preliminary results show that the siGRM1 expression induced by ponasterone A decreases endogenous GRM1 expression in our C8161 melanoma cell line. Future analysis of more siGRM1 inducible clones needs to be conducted to verify the effectiveness of the ecdysone-regulated siRNA system as a potential mechanism to suppress melanoma proliferation in vitro and in vivo. |