bc10: A novel human bladder cancer-associated protein with a conserved genomic structure downregulated in invasive cancer.

To identify novel genes that may be associated with the invasive phenotype of bladder cancer, we compared the mRNA expression profiles of fresh noninvasive (grade II, Ta) and invasive (grade III, T2-T4) human transitional cell carcinomas (TCCs) by mRNA differential display. Using this approach, we isolated a novel gene, designated bc10 (bladder cancer, Mr 10 kDa) that was exclusively expressed in the noninvasive lesions as judged by reverse transcriptase polymerase chain reaction analysis of a panel of 30 grade II, Ta and grade III, T2-T4 TCCs. The full-length bc10 cDNA contains a complete open reading frame (ORF) of 263 bp and encodes a protein composed of 87 amino acids that has no homology to any of the known protein families. Transient expression of bc10 cDNA in COS1 cells yielded a primary translation product with an apparent Mr of 9.8 kDa and pI of 6.7, in agreement with the theoretical calculated value. Comparison of mouse and human bc10 genomic loci revealed an intronless organization of the coding region in both species as well as a highly conserved structure having 91% and 100% identity at the DNA (coding region) and protein levels, respectively. Southern analysis did not reveal gross DNA rearrangements within the bc10 genomic locus in the invasive tumors, implying that the differential expression of the gene most likely reflects alterations in messenger expression (transcription and/or mRNA decay). The downregulation of this novel marker in invasive tumors suggests a putative role in bladder cancer progression. Copyright 2002 Wiley-Liss, Inc.