Retinoid signaling in immortalized and carcinoma-derived human uroepithelial cells

Mol Cell Endocrinol. 1999 Feb 25;148(1-2):55-65. doi: 10.1016/s0303-7207(98)00235-4.

Abstract

This paper investigates the presence and functionality of retinoid signaling pathways in human urinary bladder carcinoma and SV40-immortalized uroepithelial cell lines. Only two of eight cell lines were proliferation-inhibited by 10 microM of either all-trans or 13-cis-retinoic acid. Transactivation of the CAT gene under control of a retinoid-responsive element demonstrated functionality of the signaling pathway in both sensitive cell lines and four of six resistant cell lines. Relative RT-PCR analysis of a panel of retinoid-responsive and inducible genes demonstrated changes in expression levels of all the genes in response to-retinoic acid treatment together with numerous aberrations dysregulations. We conclude that retinoid signaling may be a target for inactivation during tumorigenesis by uncoupling gene expression, proliferation and differentiation. Therefore retinoids are more likely to be effective for chemoprevention than for treatment of bladder carcinomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Cell Line, Transformed
  • Chloramphenicol O-Acetyltransferase / genetics
  • Humans
  • Papilloma
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Retinoic Acid Receptor alpha
  • Retinoids / toxicity*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Simian virus 40
  • Transcription, Genetic / drug effects
  • Transcriptional Activation*
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms
  • Urothelium / cytology
  • Urothelium / drug effects*
  • Urothelium / physiology

Substances

  • RARA protein, human
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinoids
  • retinoic acid receptor beta
  • retinoic acid receptor gamma
  • Chloramphenicol O-Acetyltransferase