Identification of genes correlated with early-stage bladder cancer progression

Cancer Prev Res (Phila). 2010 Jun;3(6):776-86. doi: 10.1158/1940-6207.CAPR-09-0189. Epub 2010 May 25.


Transitional cell carcinoma (TCC) of the bladder ranks fourth in incidence of all cancers in the developed world, yet the mechanisms of its origin and progression remain poorly understood. There are also few useful diagnostic or prognostic biomarkers for this disease. We have combined a transgenic mouse model for invasive bladder cancer (UPII-SV40Tag mice) with DNA microarray technology to determine molecular mechanisms involved in early TCC development and to identify new biomarkers for detection, diagnosis, and prognosis of TCC. We have identified genes that are differentially expressed between the bladders of UPII-SV40Tag mice and their age-matched wild-type littermates at 3, 6, 20, and 30 weeks of age. These are ages that correspond to premalignant, carcinoma in situ, and early-stage and later stage invasive TCC, respectively. Our preliminary analysis of the microarray data sets has revealed approximately 1,900 unique genes differentially expressed (> or =3-fold difference at one or more time points) between wild-type and UPII-SV40Tag urothelium during the time course of tumor development. Among these, there were a high proportion of cell cycle regulatory genes and a proliferation signaling genes that are more strongly expressed in the UPII-SV40Tag bladder urothelium. We show that several of the genes upregulated in UPII-SV40Tag urothelium, including RacGAP1, PCNA, and Hmmr, are expressed at high levels in superficial bladder TCC patient samples. These findings provide insight into the earliest events in the development of bladder TCC as well as identify several promising early-stage biomarkers.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Carcinoma in Situ / genetics*
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Transitional Cell / genetics*
  • Carcinoma, Transitional Cell / metabolism
  • Carcinoma, Transitional Cell / pathology
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics
  • Disease Models, Animal
  • Disease Progression
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks
  • Genes, Neoplasm*
  • Humans
  • Hyperplasia
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Transgenic
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Precancerous Conditions / genetics
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Urinary Bladder Diseases / genetics
  • Urinary Bladder Diseases / metabolism
  • Urinary Bladder Diseases / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology
  • Urothelium / metabolism
  • Urothelium / pathology


  • Cell Cycle Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Neoplasm