Abstract:
:Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase that is frequently over-expressed in human cancers and is associated with tumorigenesis, and increased tumor proliferation and progression. Also found in breast tumors with high levels is B-Myb, a transcription factor whose expression is activated by E2F1/3 at the late G1 phase and the level is sustained through the S phase. Recent reports suggest a casual correlation between EGFR and B-Myb expression in primary breast carcinomas. However, the mechanism for such co-expression remains un-investigated. Here, we report that EGFR is important for B-Myb expression and the underlying mechanism involves cooperated effects from EGFR and E2F1. EGF stimulation and forced expression of EGFR significantly increase B-Myb gene activity and such increase occurs in the G1 phase. EGF-induced B-Myb expression was not significantly suppressed following inhibition of PI-3K and ERK, two major EGFR downstream pathways. In contrast, we observed EGF-induced in vivo association of nuclear EGFR to the B-Myb promoter and the association is only detected at the G1/S phase and is abolished by EGFR kinase inhibitor. As EGFR lacks DNA-binding domain but contains transactivational activity and E2F1 activates B-Myb expression in the G1/S phase, we further reasoned that nuclear EGFR might cooperate with E2F1 leading to activation of B-Myb. Indeed, we found that EGFR co-immunoprecipitated with E2F1 in an EGF-dependent manner and that EGF activated in vivo binding of E2F1 to the B-Myb promoter. Consistently, forced expression of both EGFR and E2F1 in EGFR-null CHO cells greatly enhanced B-Myb promoter activity, compared to the vector control and expression of EGFR or E2F1 alone. Promoter mutagenesis studies showed that EGF-induced activation of B-Myb promoter required both E2F and EGFR target sites. In summary, our data suggest that deregulated EGFR signaling pathway facilitate tumor cell proliferation partly via EGFR interaction with E2F1 and subsequent activation of B-Myb gene expression.
journal_name
Mol Carcinogjournal_title
Molecular carcinogenesisauthors
Hanada N,Lo HW,Day CP,Pan Y,Nakajima Y,Hung MCdoi
10.1002/mc.20147subject
Has Abstractpub_date
2006-01-01 00:00:00pages
10-7issue
1eissn
0899-1987issn
1098-2744journal_volume
45pub_type
杂志文章abstract::Heterocyclic amines present in cooked foods are known to produce colon tumors in F344 rats at a high incidence, indicating the possibility of involvement of ras gene activation in colon carcinogenesis in rats as in humans. We examined mutations at codons 12, 13, and 61 of the Ki-ras, Ha-ras, and N-ras genes by polymer...
journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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journal_title:Molecular carcinogenesis
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更新日期:1992-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:2013-06-01 00:00:00
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journal_title:Molecular carcinogenesis
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更新日期:2008-02-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:2012-03-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940050307
更新日期:1992-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22827
更新日期:2018-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20393
更新日期:2008-05-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
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更新日期:1999-01-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22834
更新日期:2018-09-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22149
更新日期:2015-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22475
更新日期:2017-01-01 00:00:00
abstract::To study the possible involvement of DNA damage in cell transformation induced by estrogens, we examined whether DNA adduct formation is elicited in cultured Syrian hamster embryo (SHE) cells treated with estrogens and their derivatives by means of the 32P-postlabeling assay. Morphological transformation of the cells ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(SICI)1098-2744(199607)16:3<149::AID-MC5>3
更新日期:1996-07-01 00:00:00
abstract::Recent evidence suggests that the A allele of the ornithine decarboxylase (ODC) gene is a genetic risk factor for prostate cancer. ODC is a target gene of the highly polymorphic androgen receptor (AR) gene, short alleles of which have been associated in some studies with increased prostate cancer risk. We determined O...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20047
更新日期:2004-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1002/mc.22928
更新日期:2019-02-01 00:00:00
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更新日期:2019-07-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/(sici)1098-2744(199711)20:3<298::aid-mc6>3
更新日期:1997-11-01 00:00:00
abstract::Angelica gigas Nakai (AGN) root ethanol extract exerts anti-cancer activity in several allograft and xenograft models. Here we examined its chemopreventive efficacy through gavage administration against primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Male C57BL/6 TRAMP mice and...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.22230
更新日期:2015-12-01 00:00:00
abstract::Overexpression of Fas ligand (FasL) in cancer cells elicits potential antitumor effects via recruitment of neutrophils. Conversely, FasL-expressing tumors may counterattack tumor-infiltrating lymphocytes by delivering apoptotic death signals via Fas/FasL interactions, which may lead to tumor escape. In order to distin...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21909
更新日期:2013-09-01 00:00:00
abstract::Both EGFR and HER2 are important mediators of tumorigenesis and tumor progression. Despite their best-characterized roles as plasma membrane-bound receptors, both receptors undergo nuclear translocation though the impact of this process remains unclear. In this study, we provide evidence showing that EGFR upregulates ...
journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.21936
更新日期:2013-12-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20856
更新日期:2012-11-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20095
更新日期:2005-06-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.20551
更新日期:2009-11-01 00:00:00
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journal_title:Molecular carcinogenesis
pub_type: 杂志文章
doi:10.1002/mc.2940010108
更新日期:1988-01-01 00:00:00