In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer

Jose Antonio Perdomo, Yoshio Naomoto, Minoru Haisa, Toshiyoshi Fujiwara, Madoka Hamada, Yasuo Yasuoka, Noriaki Tanaka

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Alteration of the p53 gene product is a frequent event in the progression of lung cancer. However, its importance to proliferation and response to chemoradiotherapy remains unclear. Thus, to assess its influence directly in vivo, we implanted into nude mice two kinds of human non-small- cell lung cancer (NSCLC) cells: H226br having a homozygous gene mutation in p53 (mt-p53) and H226b with intact p53 (wt-p53). We found that mt-p53 tumors grew substantially faster than wt-p53 tumors. Furthermore, treatment with cisplatin and radiation did not reduce the size of mt-p53 tumors, while wt- p53 tumors regressed by approximately 60%. Terminal-deoxytransferase-mediated dUTP-biotin nick-end labeling assay revealed apoptosis to be the mechanism responsible for the regression. Interestingly, apoptosis occurred in mt-p53 tumors although only at high doses of cisplatin and not at the magnitude detected in wt-p53 tumors. Cell labeling by staining with bromodeoxiuridine indicated that p53 is an important factor in modulating growth in NSCLC tumors. Our results are consistent with the notion that correction of a single genetic lesion enhances the therapeutic effect of chemotherapy.

Original languageEnglish
Pages (from-to)10-18
Number of pages9
JournalJournal of Cancer Research and Clinical Oncology
Volume124
Issue number1
DOIs
Publication statusPublished - 1998

Fingerprint

Non-Small Cell Lung Carcinoma
Neoplasms
Mutation
Cisplatin
Apoptosis
p53 Genes
Chemoradiotherapy
Therapeutic Uses
Biotin
Nude Mice
Lung Neoplasms
Radiation
Staining and Labeling
Drug Therapy
Growth
Genes

Keywords

  • Apoptosis
  • Chemotherapy
  • p53
  • Proliferation
  • Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer. / Perdomo, Jose Antonio; Naomoto, Yoshio; Haisa, Minoru; Fujiwara, Toshiyoshi; Hamada, Madoka; Yasuoka, Yasuo; Tanaka, Noriaki.

In: Journal of Cancer Research and Clinical Oncology, Vol. 124, No. 1, 1998, p. 10-18.

Research output: Contribution to journalArticle

Perdomo, Jose Antonio ; Naomoto, Yoshio ; Haisa, Minoru ; Fujiwara, Toshiyoshi ; Hamada, Madoka ; Yasuoka, Yasuo ; Tanaka, Noriaki. / In vivo influence of p53 status on proliferation and chemoradiosensitivity in non-small-cell lung cancer. In: Journal of Cancer Research and Clinical Oncology. 1998 ; Vol. 124, No. 1. pp. 10-18.
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