Zinc deficiency potentiates induction and progression of lingual and esophageal tumors in p53-deficient mice.

2.50
Hdl Handle:
http://hdl.handle.net/10146/64978
Title:
Zinc deficiency potentiates induction and progression of lingual and esophageal tumors in p53-deficient mice.
Authors:
Fong, Louise Y. Y.; Jiang, Yubao; Farber, John L.
Abstract:
Upper aerodigestive tract (UADT) cancer, including oral and esophageal cancer, is an important cause of cancer deaths worldwide. Patients with UADT cancer are frequently zinc deficient (ZD) and show a loss of function of the pivotal tumor suppressor gene p53. The present study examined whether zinc deficiency in collaboration with p53 insufficiency (p53+/-) promotes lingual and esophageal tumorigenesis in mice exposed to low doses of the carcinogen 4-nitroquinoline 1-oxide. In wild-type mice, ZD significantly increased the incidence of lingual and esophageal tumors from 0% in zinc sufficient (ZS) ZS:p53+/+ mice to approximately 40%. On the p53+/- background, ZD:p53+/- mice had significantly greater tumor incidence and multiplicity than ZS:p53+/- and ZD:p53+/+ mice, with a high frequency of progression to malignancy. Sixty-nine and 31% of ZD:p53+/- lingual and esophageal tumors, respectively, were squamous cell carcinoma versus 19 and 0% of ZS:p53+/- tumors (tongue, P = 0.003; esophagus, P = 0.005). Immunohistochemical analysis revealed that the increased cellular proliferation observed in preneoplastic lingual and esophageal lesions, as well as invasive carcinomas, was accompanied by overexpression of cytokeratin 14, cyclooxygenase-2 and metallothionein. In summary, a new UADT cancer model is developed in ZD:p53+/- mouse that recapitulates aspects of the human cancer and provides opportunities to probe the genetic changes intrinsic to UADT carcinogenesis and to test strategies for prevention and reversal of this deadly cancer.
Citation:
Carcinogenesis 2006, 27 (7):1489-1496
Journal:
Carcinogenesis
Issue Date:
Jul-2006
URI:
http://hdl.handle.net/10146/64978
DOI:
10.1093/carcin/bgl012
PubMed ID:
16543248
Additional Links:
http://carcin.oxfordjournals.org/cgi/content/full/27/7/1489
Type:
Article
Language:
en
Description:
KEYWORDS CLASSIFICATION: 4-Nitroquinoline-1-oxide;analysis;Animals;biosynthesis;chemically induced;Carcinogens;Cyclooxygenase 2;deficiency;Disease Models,Animal;Esophageal Neoplasms;Female;genetics;Gene Expression;Genetic Predisposition to Disease;Immunohistochemistry;Keratin-14;Keratins;Male;mechanisms of carcinogenesis;Metallothionein;Mice;Mice,Mutant Strains;pathology;Precancerous Conditions;Research;toxicity;Tongue Neoplasms;Tumor Markers,Biological;Tumor Suppressor Protein p53;Zinc.
ISSN:
0143-3334
Appears in Collections:
Articles with annotation

Full metadata record

DC FieldValue Language
dc.contributor.authorFong, Louise Y. Y.-
dc.contributor.authorJiang, Yubao-
dc.contributor.authorFarber, John L.-
dc.date.accessioned2009-04-15T12:24:03Z-
dc.date.available2009-04-15T12:24:03Z-
dc.date.issued2006-07-
dc.identifier.citationCarcinogenesis 2006, 27 (7):1489-1496en
dc.identifier.issn0143-3334-
dc.identifier.pmid16543248-
dc.identifier.doi10.1093/carcin/bgl012-
dc.identifier.urihttp://hdl.handle.net/10146/64978-
dc.descriptionKEYWORDS CLASSIFICATION: 4-Nitroquinoline-1-oxide;analysis;Animals;biosynthesis;chemically induced;Carcinogens;Cyclooxygenase 2;deficiency;Disease Models,Animal;Esophageal Neoplasms;Female;genetics;Gene Expression;Genetic Predisposition to Disease;Immunohistochemistry;Keratin-14;Keratins;Male;mechanisms of carcinogenesis;Metallothionein;Mice;Mice,Mutant Strains;pathology;Precancerous Conditions;Research;toxicity;Tongue Neoplasms;Tumor Markers,Biological;Tumor Suppressor Protein p53;Zinc.en
dc.description.abstractUpper aerodigestive tract (UADT) cancer, including oral and esophageal cancer, is an important cause of cancer deaths worldwide. Patients with UADT cancer are frequently zinc deficient (ZD) and show a loss of function of the pivotal tumor suppressor gene p53. The present study examined whether zinc deficiency in collaboration with p53 insufficiency (p53+/-) promotes lingual and esophageal tumorigenesis in mice exposed to low doses of the carcinogen 4-nitroquinoline 1-oxide. In wild-type mice, ZD significantly increased the incidence of lingual and esophageal tumors from 0% in zinc sufficient (ZS) ZS:p53+/+ mice to approximately 40%. On the p53+/- background, ZD:p53+/- mice had significantly greater tumor incidence and multiplicity than ZS:p53+/- and ZD:p53+/+ mice, with a high frequency of progression to malignancy. Sixty-nine and 31% of ZD:p53+/- lingual and esophageal tumors, respectively, were squamous cell carcinoma versus 19 and 0% of ZS:p53+/- tumors (tongue, P = 0.003; esophagus, P = 0.005). Immunohistochemical analysis revealed that the increased cellular proliferation observed in preneoplastic lingual and esophageal lesions, as well as invasive carcinomas, was accompanied by overexpression of cytokeratin 14, cyclooxygenase-2 and metallothionein. In summary, a new UADT cancer model is developed in ZD:p53+/- mouse that recapitulates aspects of the human cancer and provides opportunities to probe the genetic changes intrinsic to UADT carcinogenesis and to test strategies for prevention and reversal of this deadly cancer.en
dc.language.isoenen
dc.relation.urlhttp://carcin.oxfordjournals.org/cgi/content/full/27/7/1489en
dc.subject.mesh4-Nitroquinoline-1-oxide-
dc.subject.meshAnimals-
dc.subject.meshCarcinogens-
dc.subject.meshCyclooxygenase 2-
dc.subject.meshDisease Models, Animal-
dc.subject.meshEsophageal Neoplasms-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKeratin-14-
dc.subject.meshKeratins-
dc.subject.meshMale-
dc.subject.meshMetallothionein-
dc.subject.meshMice-
dc.subject.meshMice, Mutant Strains-
dc.subject.meshPrecancerous Conditions-
dc.subject.meshTongue Neoplasms-
dc.subject.meshTumor Markers, Biological-
dc.subject.meshTumor Suppressor Protein p53-
dc.subject.meshZinc-
dc.titleZinc deficiency potentiates induction and progression of lingual and esophageal tumors in p53-deficient mice.en
dc.typeArticleen
dc.identifier.journalCarcinogenesisen

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