Expression of transitional cell-specific genes, uroplakin Ia and II, in bladder cancer: detection of circulating cancer cells in the peripheral blood of metastatic patients

Int J Urol. 1999 Jun;6(6):286-92. doi: 10.1046/j.1442-2042.1999.00064.x.

Abstract

Background: Uroplakins (UP), urothelium-specific transmembrane proteins, are present only in urothelia and may be good candidates as tumor markers specific for transitional cell carcinomas (TCC). We investigated the expression of UP-Ia and UP-II genes in the tissues and peripheral blood of patients with TCC.

Methods: We investigated UP-Ia and UP-II gene expression in tissues from 12 patients with TCC by reverse transcription-polymerase chain reaction (RT-PCR). HT1197, a TCC cell line, was used as an indicated cell line to assess a detection system for the UP-II gene-expressing cancer cells by nested RT-PCR. We also investigated UP-II gene expression in the peripheral blood of 12 other patients with TCC by nested RT-PCR.

Results: Prior to the investigation of UP-Ia and UP-II gene expression, a partial nucleotide sequence of human UP-II gene cDNA was determined to prepare the primers for RT-PCR. Uroplakin genes were expressed in both cancerous and non-cancerous urothelia taken from all patients examined by RT-PCR. The detection sensitivity of our assay showed that one cancer cell could be detected in 5 mL peripheral blood. UP-II gene-expression was detected in the peripheral blood from all three patients with metastatic TCC but not from the nine patients with non-metastatic TCC nor the three healthy volunteers.

Conclusions: Uroplakins may be employed as tumor markers for transitional cell cancer, because they are highly conserved and well expressed, not only in non-cancerous cells but also in cancer cells. Furthermore, detection of UP-II gene expression in blood by nested RT-PCR may provide helpful information in the diagnosis and management of TCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amino Acid Sequence
  • Base Sequence
  • Biomarkers, Tumor / blood
  • Carcinoma, Transitional Cell / genetics
  • Carcinoma, Transitional Cell / metabolism*
  • Carcinoma, Transitional Cell / pathology
  • DNA, Complementary / genetics
  • Female
  • Humans
  • Male
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / genetics
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / blood
  • Membrane Proteins / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Predictive Value of Tests
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sensitivity and Specificity
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / metabolism*
  • Urinary Bladder Neoplasms / pathology
  • Uroplakin II
  • Uroplakin Ia

Substances

  • Biomarkers, Tumor
  • DNA, Complementary
  • Membrane Glycoproteins
  • Membrane Proteins
  • UPK1A protein, human
  • UPK2 protein, human
  • Uroplakin II
  • Uroplakin Ia

Associated data

  • GENBANK/AB009454