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Author |
Nicol, C.J.; Yoon, M.; Ward, J.M.; Yamashita, M.; Fukamachi, K.; Peters, J.M.; Gonzalez, F.J. |
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Title |
PPARgamma influences susceptibility to DMBA-induced mammary, ovarian and skin carcinogenesis |
Type |
Journal Article |
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Year |
2004 |
Publication |
Carcinogenesis |
Abbreviated Journal |
Carcinogenesis |
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Volume |
25 |
Issue |
9 |
Pages |
1747-1755 |
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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 |
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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. |
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Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA |
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English |
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ISSN |
0143-3334 |
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Notes |
PMID:15073042 |
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no |
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Call Number |
refbase @ user @ |
Serial |
76 |
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Author |
Breen, M.; Downs, P.; Irvin, Z.; Bell, K. |
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Title |
Intrageneric amplification of horse microsatellite markers with emphasis on the Przewalski's horse (E. przewalskii) |
Type |
Journal Article |
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Year |
1994 |
Publication |
Animal Genetics |
Abbreviated Journal |
Anim Genet |
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Volume |
25 |
Issue |
6 |
Pages |
401-405 |
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Keywords |
Animals; DNA, Satellite/*genetics; *Gene Amplification; Gene Frequency; *Genetic Markers; Heterozygote; Horses/*genetics; Species Specificity |
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Abstract |
Primer sequences flanking 13 microsatellite loci isolated from the domestic horse (E. caballus) were successfully used to amplify homologous loci in the Przewalski's horse (E. przewalskii). The results demonstrate that the level of polymorphism at all 13 loci in the Przewalski's horse was comparable to that in the domestic horse and the overall exclusion probability in the Przewalski's horse was calculated to be 0.9994. The results suggest that it should be possible to use E. caballus-derived microsatellite markers to provide parentage verification and additional valuable information to the captive management of E. przewalskii. The ability to amplify corresponding loci in the remaining five species of the genus was also confirmed, illustrating the general application of markers isolated from the domestic horse to the evaluation of polymorphism in the other six species of the genus. |
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Australian Equine Blood Typing Research Laboratory, University of Queensland, St Lucia |
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English |
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0268-9146 |
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Notes |
PMID:7695120 |
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Call Number |
Equine Behaviour @ team @ |
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2246 |
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