RGS-5 expression is restricted to angiogenic vessels and is up-regulated early during multistep tumorigenesis. RGS-5 transcripts are visualized using in situ hybridization on paraffin (A) or frozen tissue sections (B-F) and counterstained with methyl green. (A) RGS-5⁺ tumor blood vessel (original magnification × 25). In the same transgenic animal a normal islet of Langerhans (B, original magnification × 16) and a hyperplastic islet (C, original magnification × 12.5) are negative for RGS-5. (D) First RGS-5 signals are detected in early angiogenic islets (original magnification × 12.5) and the number of signals increases continuously in late angiogenic islets (E, × 10) and highly vascularized, solid tumors (F, original magnification × 5). Tumor vessels (arrows) can be distinguished from “blood lakes” (arrowheads), tumor cell–lined cavities, which do not participate in the blood circulation. Dotted lines indicate islet boundaries.