Transcriptional Activation of the Human C-Myc Gene by Simian Virus 40 Large T Antigen without Binding to p53 and RB Proteins in the Transient Expression System

Shimazu, Tsutomu; Takada, Shinako; Ishida, Susumu; Ueno, Yoshio; Koike, Katsuro

doi:10.1006/bbrc.1997.6761

Cited by 3 publications

(3 citation statements)

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“…Transcriptional activation of the Myc promoter by SVLT has been described and is probably E2F-dependent. 51,52 Interestingly, overexpression of Myc has been reported in 50% of human ULMs (6 of 12) and ULMs (11 of 23). 53 The same percentage of human ULMS (50.9%; 29 of 57) exhibited p53 overexpression, whereas leiomyomas lacked this feature.…”

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confidence: 99%

A Mouse Model of Uterine Leiomyosarcoma

Politi

Szabolcs

Fisher

et al. 2004

The American Journal of Pathology

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We are using an approach that is based on the cre/ loxP recombination process and involves a binary system of Cre-producing and Cre-responding transgenic mice to achieve ubiquitous or tissue-specific expression of oncoproteins. To develop mouse models of tumorigenesis, Cre-producers are mated with responder animals carrying a dormant oncogene targeted into the 3 untranslated region of the locus encoding cytoplasmic ␤-actin (actin cassette). Production of oncoprotein from a bicistronic message is accomplished in bitransgenic progeny by Cre-mediated excision of a segment flanked by loxP sites that is located upstream from the oncogenic sequence. Widespread Cre-dependent activation and expression of an actin-cassette transgene encoding the T antigens of the SV40 early region (SVER) commencing in embryos was compatible with normal development and did not impair viability. However, at ϳ3 months of age, all female animals developed massive uterine leiomyosarcomas, whereas practically all males exhibited enormously enlarged seminal vesicles because of pronounced hyperplasia of the smooth muscle layers. In addition, because of smooth muscle hyperproliferation, marked dilation of the gallbladder was observed in mice of both sexes. To begin exploring aberrant signaling events in the SVER-triggered tumorigenic pathways, we analyzed the expression profile of leiomyosarcomas by DNA microarray analysis.

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confidence: 99%

A Mouse Model of Uterine Leiomyosarcoma

Politi

Szabolcs

Fisher

et al. 2004

The American Journal of Pathology

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“…Studies on c-myc/SV40Tag bitransgenic mice have provided intriguing insights into concerning the underlying biology of the c-myc/SV40Tag bitransgenics synergy. Shimazu et al [4] reported that c-myc gene expression was activated by SV40 large T antigen. Thus, although the mechanism of the c-myc/SV40Tag synergy may be complex, the findings in the c-myc/SV40Tag bitransgenics brain tumor model strongly suggest that protection from c-myc-induced apoptosis might be obtained because of the ability of SV40Tag and that SV40Tag collaborates with c-myc to promote the brain tumor development.…”

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confidence: 99%

“…The tumor incidence rate was also low. Shimazu et al [4] reported transcriptional activation of the human c-myc promoter by simian virus 40 (SV40) large T antigen without binding to p53 and RB proteins in the transient expression system. Koch et al [5] showed that for association with SV40 large T antigen the functionally important myc-box II region was required suggesting that there is synergetic between SV40Tag and c-myc.…”

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Deregulation of c-myc and SV40Tag causing brain tumor in mice

Zhu

Zhang

et al. 2007

Chin. Sci. Bull.

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Deregulated expressions of both c-myc and simian virus 40 large T antigen (SV40Tag) are consistent features of lots of tumors. To investigate whether the expression of c-myc and SV40Tag in mouse might help develop a model of human tumor, we generated c-myc transgenics by inserting human c-myc gene into pTRE2 of Tet-On system. We obtained conditional expression of SV40Tag transgenics by the Tet-On system from Yangzhou University. Crossing the c-myc transgenic mouse with the SV40Tag transgenic mice to generate bitransgenics we got double-transgenic mice expressing c-myc and SV40Tag by the Tet-On system. After being treated with doxycycline continuously, single-transgenic SV40Tag mice developed brain tumor infrequently (3 of 84, 3.6%) with a long onset (185 d on average). In contrast, double-transgenic c-myc/SV40Tag mice developed brain tumor with a short onset (96 days on average) and a 41% brain tumor incidence rate (7 of 17, 41%). This tumor was assumed to be medulloblastoma. Our experiments suggest that deregulated expression of c-myc and SV40Tag in brain might generate a mouse model of human brain tumor that recapitulates some features of human medulloblastoma. transgenic, SV40Tag, tumor

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