Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer

I. Vannini, W. Zoli, A. Tesei, M. Rosetti, P. Sansone, G. Storci, A. Passardi, I. Massa, M. Ricci, D. Gusolfino, F. Fabbri, P. Ulivi, G. Brigliadori, D. Amadori, M. Bonafe

Research output: Contribution to journalArticle

Abstract

Background: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. Methods: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. Results: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. Conclusion: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.

Original languageEnglish
Pages (from-to)145-151
Number of pages7
JournalTumor Biology
Volume29
Issue number3
DOIs
Publication statusPublished - Sep 2008

Fingerprint

Codon
Arginine
Cell Survival
Alleles
Breast Neoplasms
Proline
Drug Resistance
Cell Death
In Vitro Techniques
Cell Hypoxia
Neoplasms
Transfection
Genotype
Survival
Genes

Keywords

  • Advanced breast cancer
  • BCRP-I
  • Hypoxia
  • Normoxia
  • p53 codon 72 polymorphism

ASJC Scopus subject areas

  • Cancer Research

Cite this

Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer. / Vannini, I.; Zoli, W.; Tesei, A.; Rosetti, M.; Sansone, P.; Storci, G.; Passardi, A.; Massa, I.; Ricci, M.; Gusolfino, D.; Fabbri, F.; Ulivi, P.; Brigliadori, G.; Amadori, D.; Bonafe, M.

In: Tumor Biology, Vol. 29, No. 3, 09.2008, p. 145-151.

Research output: Contribution to journalArticle

Vannini, I. ; Zoli, W. ; Tesei, A. ; Rosetti, M. ; Sansone, P. ; Storci, G. ; Passardi, A. ; Massa, I. ; Ricci, M. ; Gusolfino, D. ; Fabbri, F. ; Ulivi, P. ; Brigliadori, G. ; Amadori, D. ; Bonafe, M. / Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer. In: Tumor Biology. 2008 ; Vol. 29, No. 3. pp. 145-151.
@article{1a782cc804f54e1baadd0ffcbcf74498,
title = "Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer",
abstract = "Background: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. Methods: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. Results: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. Conclusion: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.",
keywords = "Advanced breast cancer, BCRP-I, Hypoxia, Normoxia, p53 codon 72 polymorphism",
author = "I. Vannini and W. Zoli and A. Tesei and M. Rosetti and P. Sansone and G. Storci and A. Passardi and I. Massa and M. Ricci and D. Gusolfino and F. Fabbri and P. Ulivi and G. Brigliadori and D. Amadori and M. Bonafe",
year = "2008",
month = "9",
doi = "10.1159/000143400",
language = "English",
volume = "29",
pages = "145--151",
journal = "Tumor Biology",
issn = "1010-4283",
publisher = "Springer Netherlands",
number = "3",

}

TY - JOUR

T1 - Role of p53 codon 72 arginine allele in cell survival in vitro and in the clinical outcome of patients with advanced breast cancer

AU - Vannini, I.

AU - Zoli, W.

AU - Tesei, A.

AU - Rosetti, M.

AU - Sansone, P.

AU - Storci, G.

AU - Passardi, A.

AU - Massa, I.

AU - Ricci, M.

AU - Gusolfino, D.

AU - Fabbri, F.

AU - Ulivi, P.

AU - Brigliadori, G.

AU - Amadori, D.

AU - Bonafe, M.

PY - 2008/9

Y1 - 2008/9

N2 - Background: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. Methods: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. Results: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. Conclusion: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.

AB - Background: The p53 codon 72 polymorphism, which results in either an arginine or proline residue, plays a different role in vitro and in vivo in cell survival and drug resistance. We verified, in vitro, the impact of the arginine allele on cell survival under normoxia and hypoxia, and investigated in vivo the role of p53 codon 72 arginine homozygosity in the clinical outcome of advanced breast cancer patients. Methods: Tumors at advanced stages grow in vivo in a hypoxic environment, and we mimicked such conditions in vitro using p53 null breast cancer cells transfected with either the arginine or proline allele. We also analyzed in vivo the p53 codon 72 genotype status of advanced breast cancer patients. Results: In vitro transfection of the arginine allele induced higher cell death under normoxia, whereas cell death was greater in proline-transfected cells under hypoxia. The arginine allele upregulated BCRP-I, a hypoxia response gene, which increases drug resistance. Metastatic breast cancer patients homozygous for arginine had a significantly shorter time to progression and overall survival than those with heterozygous arginine/proline tumors. Conclusion: We provide a molecular explanation for the association of the arginine allele with tumor aggressiveness and treatment resistance in advanced breast cancer.

KW - Advanced breast cancer

KW - BCRP-I

KW - Hypoxia

KW - Normoxia

KW - p53 codon 72 polymorphism

UR - http://www.scopus.com/inward/record.url?scp=46449123125&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46449123125&partnerID=8YFLogxK

U2 - 10.1159/000143400

DO - 10.1159/000143400

M3 - Article

C2 - 18612219

AN - SCOPUS:46449123125

VL - 29

SP - 145

EP - 151

JO - Tumor Biology

JF - Tumor Biology

SN - 1010-4283

IS - 3

ER -