12 October 2007
When barriers stem new roads
In vivo molecular BLI is rapidly becoming a standard method for measuring gene expression changes in normal tissues, cancer, and specific cell populations, such as stem cells. The principal gene reporter involved in BLI is firefly luciferase that, by catalyzing the oxidation of D-luciferin, emits yellow light. Although in reporter systems luciferase is directly expressed by the cell, its substrate luciferin must be added by external sources. For instance, in transgenic luciferase mice, luciferin is injected intraperitoneally, where it is thought to enter in the bloodstream reaching almost every cell of the organism. But some barriers need to be accounted. When Yimao Zhang from Johns Hopkins Medical Institution, was studying inhibitors of tumor promoting hedgehog signaling pathway, he uncovered that luciferin uptake by the cells is influenced by cell expression of the ABC transporter family member ABCG2/BCRP. In the Vol 67 No 19 of Cancer Research (the most frequently cited cancer journal in the world) Zhang and colleagues show that D-luciferin is a substrate for ABCG2/BCRP. Because any event that changes the activity of this transporter can substantially alter cell-based or in vivo bioluminescent imaging endpoints independent of other physiologic processes under investigation, this work confirm once again that drug-resistence gene modulation must be considered in BLI studies. To be optimist, better remember that side-effects in developing technologies could give new hints: "why don't establish the feseability of novel high-throughput methods for identifying new ABCG2 inhibitors just by bioluminescence imaging?" Said Zhang...
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