Radiation-induced gadd45 expression correlates with clinical response to radiotherapy of cervical carcinoma

Int J Radiat Oncol Biol Phys. 2000 Jan 15;46(2):411-6. doi: 10.1016/s0360-3016(99)00459-9.

Abstract

Background: Recent work has identified a category of genes devoted to the control of genomic stability and prevention of cellular evolution. They encode components of cell cycle checkpoint, i.e., regulatory pathways committed to ordered cell cycle transition and fidelity of replicated DNA under adverse environmental conditions, such as those following exposure to genotoxic agents. Gadd45 belongs to the class II family of DNA damage-inducible (DDI) gene, and its role in DNA repair has been proved in many experimental models. The aim of our study was to correlate gadd45 radio-induction with the responsiveness to radiotherapy of cervical carcinomas, a type of cancer most commonly treated with radiotherapy alone.

Methods: By means of a competitive polymerase chain reaction strategy, we compared in 14 patients the gene expression levels before and during external beam radiotherapy, when a dose ranging from 18 to 25 Gy was delivered to the target.

Results: We found a correlation between the lack of gadd45 induction and a good clinical response to radiotherapy, in terms of both local control and disease-free survival.

Conclusion: Our results support the measure of the induction of gadd45, and possibly of other genes required for regulated G1-S checkpoint, as a method useful for prognostic evaluation of cervical carcinoma patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biopsy
  • Carcinoma / genetics*
  • Carcinoma / pathology
  • Carcinoma / radiotherapy*
  • Cervix Uteri / pathology
  • DNA Repair*
  • Female
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Genes, p53 / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasm Proteins / radiation effects*
  • Polymerase Chain Reaction / methods
  • Proteins / genetics
  • Proteins / metabolism
  • Proteins / radiation effects*
  • Sequence Analysis, DNA
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • GADD45 protein
  • Intracellular Signaling Peptides and Proteins
  • Neoplasm Proteins
  • Proteins