The potential significance of Lutheran blood group antigen in human urothelial carcinogenesis
aDepartment of Pathology, bMicrobiology and Immunology, cParasitology, dUrology, eCollege of Medicine; Institute of Molecular Medicine, National Cheng Kung University, Tainan, Taiwan
AIM: To identify novel gene involved in human bladder carcinogenesis.METHODS: We compared the expression profiles of early-and advanced stages of bladder cancer cell lines using cDNA microarray containing 8,000 known genes. Real-time polymerase chain reaction (RT-PCR) was used to confirm the expression difference of target genes in 6 uroepithelial cell lines. Then we evaluated the biological effects of one of candidate genes using transient expression system. The prevalence in primary tumors was also examined to confirm its clinical implication. RESULTS: Lutheran blood group antigen (Lu) was one of the molecular targets differentially expressed in our model. RT-PCR revealed a trend toward positive association of Lu expression with progression of uroepithelial cell lines, except for T24 cells. Constitutive expression of Lu in a NIH3T3 cells (NIH-Lu11). did not provide growth advantage in vitro after addition of specific ligand-laminin 10/11 (p = 0.55). However, NIH-Lu11 formed subcutaneous tumor in vivo after inoculation for two weeks. Immunocytochemical staining revealed membranous localization of the Lu protein product in the primary transitional cell carcinoma of the bladder (9/18), and ureter or renal pelvis (15/37). Overexpression of Lu tends to positively correlate with clinical metastasis (p = 0.05) or larger tumors (greater than 3 cm). CONCLUSIONS: Activation of laminin/Lu pathway may play a positive role in the progression of urothelial carcinoma, thus may become a potential molecular target in the design of therapy for human bladder cancer.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in poster session 892 (Susceptibility genes).