To determine genes and transcription factors involved in angiogenesis and lymphoangiogenesis. For this purpose, we are using four transgenic mouse models of bladder cancer and inflammation to define the bladder transcriptome during cancer development and in response to BCG therapy. Cutting edge molecular techniques such as suppression subtractive hybridization (SSH) in combination with cDNA arrays are being used to select organ- and disease-specific genes and promoters.

1. To define the experimental bladder cancer transcriptome. For this purpose we are using high throughput technologies (Suppression Subtractive Hybridization combined with custom cDNA arrays) to determine bladder transcriptome during cancer progression in SV40-UPII mice (see below).



2. To define the role of NF-kB, angiogenesis and lymphoangiogenesis in bladder cancer progression. For this purpose we are using double transgenic mice: SV40-kB-lacZ and SV40-Igk-LacZ (see below). These new transgenic mice will permit determination of key molecules involved in angiogenesis and lymphoangiogenesis.

Animal models of bladder cancer progression (SV40-UPKII and Ha-Ras-UPKII). Our laboratory has two transgenic mouse colonies expressing SV40 and Ha-Ras genes specifically in the bladder mucosa. These mice were generated by Dr. Xue-Ru Wu and are being used for determination of lymphatic vessels density (using LYVE-1 antibody) during bladder cancer progression.

Animal model for lymphatic vessel visualization (kB-LacZ). We recently reported that mice caring a LacZ reporter gene under the promoter of p105 (NF-kB) can be used to visualize lymphatic vessels (Blood 2004, 104: 3228-3230).

Animal model for blood vessel visualization (Igk-LacZ). Igk-LacZ mice have the immunoglobulin k light chain enhancer upstream of LacZ reporter gene. These mice have constitutive expression of LacZ in blood vessels.