Records |
Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
Keywords |
9,10-Dimethyl-1,2-benzanthracene/*toxicity; Animals; DNA Primers/chemistry; Disease Susceptibility; Female; Heterozygote; Humans; Mammary Neoplasms, Experimental/chemically induced/*pathology; Mice; Ovarian Neoplasms/chemically induced/*pathology; RNA, Messenger/genetics/metabolism; Receptors, Cytoplasmic and Nuclear/genetics/*physiology; Reverse Transcriptase Polymerase Chain Reaction; Skin Neoplasms/chemically induced/*pathology; Survival Rate; Transcription Factors/genetics/*physiology; Zinc Fingers |
Abstract |
Peroxisome proliferator-activated receptor gamma (PPARgamma), a member of the nuclear receptor superfamily, plays a role in adipocyte differentiation, type II diabetes, macrophage response to inflammation and is suggested to influence carcinogen-induced colon cancer. Studies done in vitro and in vivo also revealed that PPARgamma ligands might promote differentiation and/or regression of mammary tumors. To directly evaluate the role of PPARgamma in mammary carcinogenesis, PPARgamma wild-type (+/+) or heterozygous (+/-) mice were administered 1 mg 7,12-dimethylbenz[a]anthracene (DMBA) by gavage once a week for 6 weeks and followed for a total of 25 weeks. Compared with congenic PPARgamma(+/+) littermate controls, PPARgamma(+/-) mice had early evidence for increased susceptibility to DMBA-mediated carcinogenesis based on a 1.6-fold increase in the percentage of mice with skin papillomas, as well as a 1.7-fold increase in the numbers of skin papillomas per mouse (P < 0.05). Similarly, PPARgamma(+/-) mice also had a 1.5-fold decreased survival rate (P = 0.059), and a 1.7-fold increased incidence of total tumors per mouse (P < 0.01). Moreover, PPARgamma(+/-) mice had an almost 3-fold increase in mammary adenocarcinomas (P < 0.05), an over 3-fold increase in ovarian granulosa cell carcinomas (P < 0.05), an over 3-fold increase in malignant tumors (P < 0.02) and a 4.6-fold increase in metastatic incidence. These results are the first to demonstrate an increased susceptibility in vivo of PPARgamma haploinsufficiency to DMBA-mediated carcinogenesis and suggest that PPARgamma may act as a tumor modifier of skin, ovarian and breast cancers. The data also support evidence suggesting a beneficial role for PPARgamma-specific ligands in the chemoprevention of mammary, ovarian and skin carcinogenesis. |
Address |
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
Corporate Author |
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Thesis |
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Publisher |
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Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
0143-3334 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
PMID:15073042 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
76 |
Permanent link to this record |
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Author |
Harman, F.S.; Nicol, C.J.; Marin, H.E.; Ward, J.M.; Gonzalez, F.J.; Peters, J.M. |
Title |
Peroxisome proliferator-activated receptor-delta attenuates colon carcinogenesis |
Type |
Journal Article |
Year |
2004 |
Publication |
Nature medicine |
Abbreviated Journal |
Nat Med |
Volume |
10 |
Issue |
5 |
Pages |
481-483 |
Keywords |
Animals; Azoxymethane/toxicity; Colonic Neoplasms/etiology/genetics/*prevention & control; Colonic Polyps/etiology/genetics/pathology/prevention & control; Disease Models, Animal; Mice; Mice, Knockout; Mice, Mutant Strains; Phenotype; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*physiology; Transcription Factors/deficiency/genetics/*physiology |
Abstract |
Peroxisome proliferator-activated receptor-delta (PPAR-delta; also known as PPAR-beta) is expressed at high levels in colon tumors, but its contribution to colon cancer is unclear. We examined the role of PPAR-delta in colon carcinogenesis using PPAR-delta-deficient (Ppard(-/-)) mice. In both the Min mutant and chemically induced mouse models, colon polyp formation was significantly greater in mice nullizygous for PPAR-delta. In contrast to previous reports suggesting that activation of PPAR-delta potentiates colon polyp formation, here we show that PPAR-delta attenuates colon carcinogenesis. |
Address |
Department of Veterinary Science and The Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802, USA. jmp21@psu.edu |
Corporate Author |
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Thesis |
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Publisher |
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Place of Publication |
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Editor |
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Language |
English |
Summary Language |
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Original Title |
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Series Editor |
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Series Title |
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Abbreviated Series Title |
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Series Volume |
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Series Issue |
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Edition |
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ISSN |
1078-8956 |
ISBN |
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Medium |
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Area |
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Expedition |
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Conference |
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Notes |
PMID:15048110 |
Approved |
no |
Call Number |
refbase @ user @ |
Serial |
77 |
Permanent link to this record |