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Bruno F. Fernandes, Shawn C. Maloney, Emilia Antecka, Sebastian Di Cesare, Tamara Granner, Miguel N. Burnier, Jr.; Sodium Butyrate (NaB) Induces KAI-1 Expression And Apoptosis In Uveal Melanoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1447.
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To date, seven metastasis suppressor genes (MSG) have been recognized to suppress metastasis without affecting primary tumor growth: CD44, MAPK4, NM23-H1, NM23-H2, KISS1, BrMS1 and KAI-1. The suppression of KAI-1 in different types of cancer has been linked with decreased survival time due to an increased capability of cancer cells to invade tissues and to metastasize.We previously showed a strong correlation between decreased immunoexpression of KAI-1 and increased incidence of metastasis in uveal melanoma (UM). In the present study, we investigated the effect of KAI-1 overexpression after treatment of UM cell lines with Sodium Butyrate (NaB).
Basal expression of KAI-1 was studied by confocal immunostaining and Western blot in 4 different UM cell lines (92.1, SP6.5, OCM-1 & MKT-BR). The 92.1 cell line was chosen to test the effects of sodium butyrate (NaB) in KAI-1 levels. A proliferation assay and TUNEL staining were performed at different concentrations of NaB. RT-PCR was used to confirm that the drug was able to cause an increase in KAI-1.
Under the confocal microscope, no significant differences in staining intensity were seen among the 4 studied cell lines. However, Western Blot revealed that 92.1, the most malignant one, had the lowest levels of KAI-1. Treatment of this cell line with NaB affected cell viability at the concentration of 1mM. Lower concentrations of the drug had no effect when comparing to the control. The observed decreased survival of the treated UM cell line correlated with induction of apoptosis, as seen by TUNEL staining. RT-PCR confirmed elevated levels of KAI-1 expression after treatment with 1mM but not with lower concentrations of the drug.
We observed an inversed correlation between the levels of KAI-1 expression and metastatic potential in the UM cell line. The cell line with the highest metastatic potential (92.1) displayed the lowest concentration of KAI-1. NaB was able to increase the expression of this MSG and cause a reduction in the proliferation rates by inducing apoptosis. These results further substantiate the use of KAI-1 as a potential therapeutic target in the treatment of UM. Re-expression of KAI in high-risk patients might prevent disease progression and prolong disease-free survival.
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