Abstract:
BACKGROUND:Persistent infection by high risk HPV types (e.g. HPV-16, -18, -31, and -45) is the main risk factor for development of cervical intraepithelial neoplasia and cervical cancer. Tumor necrosis factor (TNF) is a key mediator of epithelial cell inflammatory response and exerts a potent cytostatic effect on normal or HPV16, but not on HPV18 immortalized keratinocytes. Moreover, several cervical carcinoma-derived cell lines are resistant to TNF anti-proliferative effect suggesting that the acquisition of TNF-resistance may constitute an important step in HPV-mediated carcinogenesis. In the present study, we compared the gene expression profiles of normal and HPV16 or 18 immortalized human keratinocytes before and after treatment with TNF for 3 or 60 hours. METHODS:In this study, we determined the transcriptional changes 3 and 60 hours after TNF treatment of normal, HPV16 and HPV18 immortalized keratinocytes by microarray analysis. The expression pattern of two genes observed by microarray was confirmed by Northern Blot. NF-kappaB activation was also determined by electrophoretic mobility shift assay (EMSA) using specific oligonucleotides and nuclear protein extracts. RESULTS:We observed the differential expression of a common set of genes in two TNF-sensitive cell lines that differs from those modulated in TNF-resistant ones. This information was used to define genes whose differential expression could be associated with the differential response to TNF, such as: KLK7 (kallikrein 7), SOD2 (superoxide dismutase 2), 100P (S100 calcium binding protein P), PI3 (protease inhibitor 3, skin-derived), CSTA (cystatin A), RARRES1 (retinoic acid receptor responder 1), and LXN (latexin). The differential expression of the KLK7 and SOD2 transcripts was confirmed by Northern blot. Moreover, we observed that SOD2 expression correlates with the differential NF-kappaB activation exhibited by TNF-sensitive and TNF-resistant cells. CONCLUSION:This is the first in depth analysis of the differential effect of TNF on normal and HPV16 or HPV18 immortalized keratinocytes. Our findings may be useful for the identification of genes involved in TNF resistance acquisition and candidate genes which deregulated expression may be associated with cervical disease establishment and/or progression.
journal_name
BMC Med Genomicsjournal_title
BMC medical genomicsauthors
Termini L,Boccardo E,Esteves GH,Hirata R Jr,Martins WK,Colo AE,Neves EJ,Villa LL,Reis LFdoi
10.1186/1755-8794-1-29subject
Has Abstractpub_date
2008-06-27 00:00:00pages
29issn
1755-8794pii
1755-8794-1-29journal_volume
1pub_type
杂志文章abstract:BACKGROUND:Neuroblastoma (NB) tumors are well known for their pronounced clinical and molecular heterogeneity. The global gene expression and DNA copy number alterations have been shown to have profound differences in tumors of low or high stage and those with or without MYCN amplification. RNA splicing is an important...
journal_title:BMC medical genomics
pub_type: 杂志文章
doi:10.1186/1755-8794-4-35
更新日期:2011-04-18 00:00:00
abstract:BACKGROUND:The opioid use disorder and overdose crisis in the United States affects public health as well as social and economic welfare. While several genetic and non-genetic risk factors for opioid use disorder have been identified, many of the genetic associations have not been independently replicated, and it is no...
journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2008-11-11 00:00:00
abstract::This editorial summarizes eight research articles included in this supplement issue for the 2020 International Conference on Intelligent Biology and Medicine (ICIBM 2020) conference, that was held on August 9-10, 2020 (virtual conference), with a topic on data-driven analytics in biomedical genomics. These articles co...
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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更新日期:2011-06-30 00:00:00
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
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更新日期:2017-10-11 00:00:00
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journal_title:BMC medical genomics
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2008-12-29 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2008-09-29 00:00:00
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journal_title:BMC medical genomics
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更新日期:2019-12-20 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2020-04-23 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2011-06-07 00:00:00
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journal_title:BMC medical genomics
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更新日期:2020-09-18 00:00:00
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journal_title:BMC medical genomics
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更新日期:2009-07-23 00:00:00
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journal_title:BMC medical genomics
pub_type: 杂志文章
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更新日期:2018-02-13 00:00:00