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DC Field | Value | Language |
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dc.contributor.author | Kabil, A | - |
dc.contributor.author | Silva, E | - |
dc.contributor.author | Kortenkamp, A | - |
dc.date.accessioned | 2014-08-04T13:31:28Z | - |
dc.date.available | 2014-08-04T13:31:28Z | - |
dc.date.issued | 2008 | - |
dc.identifier.citation | Carcinogenesis, 29(10), 1862-1868, 2008 | en_US |
dc.identifier.issn | 0143-3334 | - |
dc.identifier.uri | http://carcin.oxfordjournals.org/content/29/10/1862 | en |
dc.identifier.uri | http://bura.brunel.ac.uk/handle/2438/8823 | - |
dc.description | This article is available open access through the publisher’s website. Copyright @ 2008 The Authors. | en_US |
dc.description.abstract | Reports of the ability of estrogenic agents such as 17β-estradiol (E2), estriol (E3) and bisphenol A (BPA) to induce micronuclei (MN) in MCF-7 breast cancer cells have prompted us to investigate whether these effects are linked to activation of the estrogen receptor (ER) α. Coadministration of tamoxifen and the pure ER antagonist ICI 182 780 to cells treated with E2 and E3 did not lead to significant reductions in micronucleus frequencies. Since these antiestrogens interfere with the transcriptional activity of the ER and block promotion of ER-dependent gene expression, it appears that this process is not involved in micronucleus formation. However, ER activation also triggers rapid signaling via the Src/Raf/extracellular signal-regulated kinase (Erk) pathway. When MCF-7 cells were exposed to E2 and BPA in combination with the specific kinase inhibitors pyrazolopyrimidine and 2′-amino-3′-methoxyflavone, reductions in micronucleus frequencies occurred. These findings suggest that the Src/Raf/Erk pathway plays a role in micronucleus formation by estrogenic agents. Enhanced activation of the Src/Raf/Erk cascade disturbs the localization of Aurora B kinase to kinetochores, leading to a defective spindle checkpoint with chromosome malsegregation. Using antikinetochore CREST antibody staining, a high proportion of micronucleus containing kinetochores was observed, indicating that such processes are relevant to the induction of MN by estrogens. Our results suggest that estrogens induce MN by causing improper chromosome segregation, possibly by interfering with kinase signaling that controls the spindle checkpoint, or by inducing centrosome amplification. Our findings may have some relevance in explaining the effects of estrogens in the later stages of breast carcinogenesis. | en_US |
dc.description.sponsorship | European Commission | en_US |
dc.language | English | - |
dc.language.iso | en | en_US |
dc.publisher | Oxford University Press | en_US |
dc.subject | Breast cancer | en_US |
dc.subject | Estrogens | en_US |
dc.subject | Micronucleus formation | en_US |
dc.subject | Src/Raf/Erk signaling | en_US |
dc.title | Estrogens and genomic instability in human cancer cells-involvement of Src/Raf/Erk signaling in micronucleus formation by estrogenic chemicals | en_US |
dc.type | Article | en_US |
dc.identifier.doi | http://dx.doi.org/10.1093/carcin/bgn138 | - |
pubs.organisational-data | /Brunel | - |
pubs.organisational-data | /Brunel/Brunel Staff by College/Department/Division | - |
pubs.organisational-data | /Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences | - |
pubs.organisational-data | /Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences/Dept of Life Sciences | - |
pubs.organisational-data | /Brunel/Brunel Staff by College/Department/Division/College of Health and Life Sciences/Dept of Life Sciences/Biological Sciences | - |
pubs.organisational-data | /Brunel/Brunel Staff by Institute/Theme | - |
pubs.organisational-data | /Brunel/Brunel Staff by Institute/Theme/Institute of Environmental, Health and Societies | - |
pubs.organisational-data | /Brunel/Brunel Staff by Institute/Theme/Institute of Environmental, Health and Societies/Health and Environment | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute for Ageing Studies | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Brunel Institute of Cancer Genetics and Pharmacogenomics | - |
pubs.organisational-data | /Brunel/University Research Centres and Groups/School of Health Sciences and Social Care - URCs and Groups/Centre for Systems and Synthetic Biology | - |
Appears in Collections: | Environment Institute for the Environment |
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