Gene expression profiling and pathway analysis of superficial bladder cancer in rats.

Objectives: To reveal the gene expression profile and pathways involved in host-tumor interactions in a rat orthotopic syngeneic bladder cancer model.

Methods: Rat bladder cancer cells (AY-27 cell line) were inoculated intravesically into female Fischer rats. The bladders were analyzed at 7, 14, and 28 days by histologic examination and at 14 days with Affymetrix GeneChip with a newly developed bioinformatics program for the Kyoto Encyclopedia of Genes and Genomes (KEGG).

Results: The cancer had developed into Stage Ta and carcinoma in situ (Tis) after 7 days, Stage T1 after 14 days, and Stage T3 after 28 days in the bladder. At 14 days, >4000 genes were found to be differentially expressed and 20 KEGG pathways were actively involved in the bladder. The molecular pathway for (human) bladder cancer development was activated, and, at the same time, pathways in connection with the host immune responses were altered, including antigen processing and presentation, the T-cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, the Toll-like receptor signaling pathway, and the B-cell receptor signaling pathway. Moreover, the cell adhesion molecules associated with the immune system were upregulated, but those associated with the neural system were downregulated.

Conclusions: The bladder cancer developed aggressively despite active host immune responses. Conceivably, the cancer immunoediting process is associated with the progression of bladder cancer in this model.