Inhibition of tumor cell growth by RTP/rit42 and its responsiveness to p53 and DNA damage

Cancer Res. 1998 Oct 1;58(19):4439-44.


Through a differential screening technique, we have identified a cDNA clone with differential expression in normal versus tumor cells. This clone, designated rit42 (reduced in tumor, 42 kDa), was previously isolated as a homocysteine-inducible gene in human endothelial cells (RTP), and the same or a highly related androgen-responsive gene in mouse has also been identified. Both Northern blot analysis and in situ hybridization demonstrated a significantly diminished expression in tumor cells, including those derived from breast and prostate when compared with normal cells. It was shown that RTP/rit42 mRNA cycles with cell division, peaking at G1 and G2-M, with lower expression in S phase. The biphasic expression of RTP/rit42 mRNA was absent in tumor cells. Introduction of rit42 cDNA into human cancer cells reduced cell growth both in vitro and in nude mice. Moreover, analysis of a tetracycline-regulated p53-inducible system in null-p53 cell lines showed that RTP/rit42 mRNA expression increased concomitantly with p53 expression and followed a similar time course. In addition, DNA-damaging agents induced RTP/rit42 expression in a p53-dependent manner but independent of a p53-mediated G1 arrest. Immunofluorescence analysis of a FLAG epitope-tagged RTP/rit42 protein revealed a cytoplasmic localization pattern with redistribution to the nucleus upon DNA damage. We have localized RTP/rit42 to human chromosome 8q24.3. Taken together, these results are consistent with a growth inhibitory role for RTP/rit42, and its down-regulation may contribute to the tumor malignant phenotype.

Publication types

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

MeSH terms

  • Animals
  • Breast Neoplasms
  • Cell Cycle / physiology*
  • Cell Cycle Proteins / biosynthesis
  • Cell Cycle Proteins / genetics*
  • Cell Division
  • Cells, Cultured
  • Chromosome Mapping
  • Chromosomes, Human, Pair 8
  • DNA Damage*
  • Dactinomycin / toxicity
  • Doxorubicin / toxicity
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / physiology*
  • Female
  • Gene Library
  • Genes, p53*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Male
  • Mice
  • Mitomycin / toxicity
  • Polymerase Chain Reaction
  • Prostatic Neoplasms
  • RNA, Messenger / biosynthesis
  • Recombinant Fusion Proteins / biosynthesis
  • Transcription, Genetic*
  • Transfection
  • Tumor Cells, Cultured
  • Tumor Stem Cell Assay
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms


  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • N-myc downstream-regulated gene 1 protein
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53
  • Dactinomycin
  • Mitomycin
  • Doxorubicin