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Expert Opin. Drug Metab. Toxicol. 4, 103–120. Bioluminescent assays for ADMET 2008

Cali, J.J., Niles, A., Valley, M.P., O’Brien, M.A., Riss, T.L., and Shultz, J.

Notes: The authors of this review article highlight the use of bioluminescence as a readout for high-throughput ADME/Tox assays. They discuss three strategies for designing bioluminescent assays, using either luciferase, ATP or luciferin substrates as the limiting reagents for a luciferase-catalyzed reaction. Reporter gene assays limit the production of luciferase by tying it to a promoter or DNA regulatory region of interest. Such assays can be used to study genes that are regulated by drugs and other xenobiotics. Bioluminescent assays in which ATP is the limiting reagent of the luciferase reaction can be designed to monitor cell viability or the activity kinases. Bioluminescent assays in which the substrate is limiting can be designed so that the activity of a particular enzyme results in the production of a luciferin substrate that can, in turn, be acted upon by luciferase. (3926)

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J. Clin. Invest. 117, 206-17. The type III TGF-b receptor suppresses breast cancer progression. 2007

Dong, M., How, T., Kirkbride, K.C., Gordon, K.J., Lee, J.D., Hempel, N., Kelly, P., Moeller, B.J., Marks, J.R., and Blobe, G.C.

Notes: These authors showed that loss of the type II TGF-β receptor TGFβIII through allelic imbalance occurs during breast cancer development and increases metastatic potential. When TGFβIII expression was restored in human breast cancer cells, invasiveness, angiogenesis and metastasis were inhibited in an in vivo model system. The authors first analyzed TGFβIII mRNA levels using a cDNA array of 50 different breast cancer samples and controls. They also investigated TGFβIII protein expression levels by immunohistochemical analysis of a breast cancer tissue array containing over 250 breast cancers specimens at different stages of disease progression. Results from both analyses showed that TGFβIII expression decreased as disease progressed. The effect pf TGFβIII expression on tumor growth was investigated in a mouse model system. Murine 4T1 mammary cancer cells genetically engineered to express firefly luciferase were stably transfected with an expression vector containing TGFβIII , or a control vector. Tumor progression was then monitored in vivo by bioluminescent imaging. Cells expressing TGFβIII had delayed onset of metastasis and a reduction on the size and number of metastases compared with non-TGFβIII-expressing cells. (3617)

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