Gene expression in the lung of p53 mutant mice exposed to cigarette smoke

Alberto Izzotti, Cristina Cartiglia, Mariagrazia Longobardi, Maria Bagnasco, Andrea Merello, Ming You, Ronald A. Lubet, Silvio De Flora

Research output: Contribution to journalArticle

Abstract

We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 × A/J)F, mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor thep55 status affected the expression of the p55 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smokeexposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiptics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.

Original languageEnglish
Pages (from-to)8566-8572
Number of pages7
JournalCancer Research
Volume64
Issue number23
DOIs
Publication statusPublished - Dec 1 2004

Fingerprint

Smoke
Tobacco Products
Gene Expression
Lung
Mutation
Genes
Carcinogenesis
P-Glycoproteins
Germ-Line Mutation
Neoplasm Genes
p53 Genes
Environmental Exposure
Nuclear Proteins
Oligonucleotide Array Sequence Analysis
Tumor Suppressor Genes
Oncogenes
Cytogenetics
DNA Repair
Signal Transduction
Cell Cycle

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Izzotti, A., Cartiglia, C., Longobardi, M., Bagnasco, M., Merello, A., You, M., ... De Flora, S. (2004). Gene expression in the lung of p53 mutant mice exposed to cigarette smoke. Cancer Research, 64(23), 8566-8572. https://doi.org/10.1158/0008-5472.CAN-04-1420

Gene expression in the lung of p53 mutant mice exposed to cigarette smoke. / Izzotti, Alberto; Cartiglia, Cristina; Longobardi, Mariagrazia; Bagnasco, Maria; Merello, Andrea; You, Ming; Lubet, Ronald A.; De Flora, Silvio.

In: Cancer Research, Vol. 64, No. 23, 01.12.2004, p. 8566-8572.

Research output: Contribution to journalArticle

Izzotti, A, Cartiglia, C, Longobardi, M, Bagnasco, M, Merello, A, You, M, Lubet, RA & De Flora, S 2004, 'Gene expression in the lung of p53 mutant mice exposed to cigarette smoke', Cancer Research, vol. 64, no. 23, pp. 8566-8572. https://doi.org/10.1158/0008-5472.CAN-04-1420
Izzotti A, Cartiglia C, Longobardi M, Bagnasco M, Merello A, You M et al. Gene expression in the lung of p53 mutant mice exposed to cigarette smoke. Cancer Research. 2004 Dec 1;64(23):8566-8572. https://doi.org/10.1158/0008-5472.CAN-04-1420
Izzotti, Alberto ; Cartiglia, Cristina ; Longobardi, Mariagrazia ; Bagnasco, Maria ; Merello, Andrea ; You, Ming ; Lubet, Ronald A. ; De Flora, Silvio. / Gene expression in the lung of p53 mutant mice exposed to cigarette smoke. In: Cancer Research. 2004 ; Vol. 64, No. 23. pp. 8566-8572.
@article{697bff2159d146b984417543a3b9d75c,
title = "Gene expression in the lung of p53 mutant mice exposed to cigarette smoke",
abstract = "We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 × A/J)F, mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor thep55 status affected the expression of the p55 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smokeexposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiptics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.",
author = "Alberto Izzotti and Cristina Cartiglia and Mariagrazia Longobardi and Maria Bagnasco and Andrea Merello and Ming You and Lubet, {Ronald A.} and {De Flora}, Silvio",
year = "2004",
month = "12",
day = "1",
doi = "10.1158/0008-5472.CAN-04-1420",
language = "English",
volume = "64",
pages = "8566--8572",
journal = "Journal of Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "23",

}

TY - JOUR

T1 - Gene expression in the lung of p53 mutant mice exposed to cigarette smoke

AU - Izzotti, Alberto

AU - Cartiglia, Cristina

AU - Longobardi, Mariagrazia

AU - Bagnasco, Maria

AU - Merello, Andrea

AU - You, Ming

AU - Lubet, Ronald A.

AU - De Flora, Silvio

PY - 2004/12/1

Y1 - 2004/12/1

N2 - We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 × A/J)F, mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor thep55 status affected the expression of the p55 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smokeexposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiptics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.

AB - We showed previously that p53 mutations play a role in cigarette smoke-related carcinogenesis not only in humans but also in A/J mice. In fact, (UL53-3 × A/J)F, mice, carrying a dominant-negative germ-line p53 mutation, responded to exposure to environmental cigarette smoke more efficiently than their wild-type (wt) littermate controls in terms of molecular alterations, cytogenetic damage, and lung tumor yield. To clarify the mechanisms involved, we analyzed by cDNA array the expression of 1,185 cancer-related genes in the lung of the same mice. Neither environmental cigarette smoke nor thep55 status affected the expression of the p55 gene, but the p53 mutation strikingly increased the basal levels of p53 nuclear protein in the lung. Environmental cigarette smoke increased p53 protein levels in wt mice only. The p53 mutation enhanced the expression of positive cell cycle regulators in sham-exposed mice, which suggests a physiologic protective role of p53. In environmental cigarette smokeexposed mice, the p53 mutation resulted in a lack of induction of proapoptotic genes and in overexpression of genes involved in cell proliferation, signal transduction, angiogenesis, inflammation, and immune response. Mutant mice and wt mice reacted to environmental cigarette smoke in a similar manner regarding genes involved in metabolism of xenobiptics, multidrug resistance, and protein repair. Irrespective of the p53 status, environmental cigarette smoke poorly affected the expression of oncogenes, tumor suppressor genes, and DNA repair genes. Taken together, these findings may explain the increased susceptibility of p53 mutant mice to smoke-related alterations of intermediate biomarkers and lung carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=9244260573&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=9244260573&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-04-1420

DO - 10.1158/0008-5472.CAN-04-1420

M3 - Article

C2 - 15574763

AN - SCOPUS:9244260573

VL - 64

SP - 8566

EP - 8572

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0008-5472

IS - 23

ER -