p73 protein expression correlates with radiation-induced apoptosis in the lack of p53 response to radiation therapy for cervical cancer

Int J Radiat Oncol Biol Phys. 2008 Mar 15;70(4):1189-94. doi: 10.1016/j.ijrobp.2007.08.033.

Abstract

Purpose: p73 belongs to the p53 tumor suppressor family of genes and can inhibit cell growth in a p53-like manner by inducing apoptosis or cell cycle arrest. Here, we investigated whether p73 could compensate for impaired p53 function in apoptosis induced by radiation therapy (RT) for cervical cancer.

Methods and materials: Sixty-eight patients with squamous cell carcinoma of the cervix who received definitive RT combined with (n=37) or without (n=31) cisplatin were investigated. Biopsy specimens were excised from the cervical tumor before RT and after 9 Gy.

Results: Mean apoptosis index (AI) was 0.93% before RT and 1.97% after 9 Gy with a significant increase (p<0.001). For all patients, there was a significant correlation between p73 expression positivity after 9 Gy and AI ratio (AI after 9 Gy/AI before RT) (p=0.021). Forty-one patients were regarded as the p53-responding group according to the expression of p53 after 9 Gy, whereas the remaining 27 patients were regarded as the p53-nonresponding group. A significant correlation between p73 expression after 9 Gy and AI ratio was observed in the p53-non-responding group (p<0.001) but not in the p53-responding group (p=0.940).

Conclusion: Our results suggest that p73 plays an important role in compensating for the lack of p53 function in radiation-induced apoptosis of cervical cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use
  • Apoptosis*
  • Brachytherapy
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / radiotherapy*
  • Cisplatin / therapeutic use
  • DNA-Binding Proteins / metabolism*
  • Female
  • Genes, p53
  • Humans
  • In Situ Nick-End Labeling
  • Middle Aged
  • Nuclear Proteins / metabolism*
  • Radiation-Sensitizing Agents / therapeutic use
  • Tumor Protein p73
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins / metabolism*
  • Uterine Cervical Neoplasms / drug therapy
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / radiotherapy*

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Radiation-Sensitizing Agents
  • TP73 protein, human
  • Tumor Protein p73
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • Cisplatin