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C. Martins, S. Di Cesare, J. Isenberg, D. Faingold, B. Silvin, M. N. Burnier, Jr.; Regulation of KISS1 in Uveal Melanoma Cell Lines Treated With Imatinib Mesylate by MicroRNAs, SP1 and DRIP-130. Invest. Ophthalmol. Vis. Sci. 2010;51(13):863.
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Metastasis is the cause of death in approximately 40% of Uveal Melanoma (UM) patients within 10 years of initial diagnosis. KISS1 - a human metastasis suppressor gene -has been reported to play a role in various human malignancies, including UM. Its re-expression by micrometastatic tumor cells might have therapeutic effects on metastatic evolution. Mechanisms by which it acts or its expression is regulated are not well understood. The Sp1 co-activator complex DRIP-130 appears to play an important role as do microRNAs, small non-coding single-stranded RNAs that can regulate multiple gene targets. Imatinib mesylate (IM) is a compound that inhibits c-kit and has been shown to abrogate the development of metastatic disease. Previous studies show that KISS1 is overexpressed in UM cells treated with IM. The purpose of this study was to identify specific regulators that mediate this overexpression of KISS1 in IM treated UM cells.
Quantitative real-time PCR was used to determine mRNA transcript levels of SP1andDRIP-130in a panel of primary (92.1, SP6.5, MKT-BR, OCM-1, UW-1, and MEL 270) and metastatic (OMM1.3 and OMM1.5) UM cell lines after treatment with IM.
All cell lines treated with Imatinib mesylate had increased levels of SP1 and DRIP-130 compared to untreated controls. SP1 and DRIP-130 were increased, respectively, in MKTBR (1.5- and 4.5-fold), 92.1 (2.0- and 1.8-fold), SP6.5 (5.5- and 1.5-fold), OCM-1 (1.3- and 1.2- fold), and UW-1 (3.9- and 2.1-fold). Additionally, DRIP-130 was increased 1.3-fold in the primary UM cell line MEL270 and 4.5- and 1.5-fold in the corresponding metastatic cell lines OMM1.3 and OMM1.5, respectively.
To the best of our knowledge, this is the first study demonstrating that KISS1 regulators were induced in uveal melanoma cell lines. Considering the importance of KISS1 expression in gauging metastasis, an understanding of its transcriptional regulation may prove clinically relevant. Future studies will further investigate the significance of microRNA regulation in UM progression.
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