Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway
| dc.contributor.author | Adefuye, Anthonio O | |
| dc.contributor.author | Sales, Kurt J | |
| dc.contributor.author | Katz, Arieh A | |
| dc.date.accessioned | 2015-07-30T04:11:06Z | |
| dc.date.available | 2015-07-30T04:11:06Z | |
| dc.date.issued | 2014-08-08 | |
| dc.date.updated | 2015-04-28T18:01:24Z | |
| dc.description.abstract | Abstract Background Cervical cancer is a chronic inflammatory disease of multifactorial etiology usually presenting in sexually active women. Exposure of neoplastic cervical epithelial cells to seminal plasma (SP) has been shown to promote the growth of cancer cells in vitro and tumors in vivo by inducing the expression of inflammatory mediators including pro-inflammatory cytokines. IL-1α is a pleotropic pro-inflammatory cytokine induced in several human cancers and has been associated with virulent tumor phenotype and poorer prognosis. Here we investigated the expression of IL-1α in cervical cancer, the role of SP in the regulation of IL-1α in neoplastic cervical epithelial cells and the molecular mechanism underlying this regulation. Methods and results Real-time quantitative RT-PCR confirmed the elevated expression of IL-1α mRNA in cervical squamous cell carcinoma and adenocarcinoma tissue explants, compared with normal cervix. Using immunohistochemistry, IL-1α was localized to the neoplastically transformed squamous, columnar and glandular epithelium in all cases of squamous cell carcinoma and adenocarcinomas explants studied. We found that SP induced the expression of IL-α in both normal and neoplastic cervical tissue explants. Employing HeLa (adenocarcinoma) cell line as a model system we identified PGE2 and EGF as possible ligands responsible for SP-mediated induction of IL-1α in these neoplastic cells. In addition, we showed that SP activates EP2/EGFR/PI3kinase-Akt signaling to induce IL-1α mRNA and protein expression. Furthermore, we demonstrate that in normal cervical tissue explants the induction of IL-1α by SP is via the activation of EP2/EGFR/PI3 kinase-Akt signaling. Conclusion SP-mediated induction of IL-1α in normal and neoplastic cervical epithelial cells suggests that SP may promote cervical inflammation as well as progression of cervical cancer in sexually active women. | |
| dc.identifier.apacitation | Adefuye, A. O., Sales, K. J., & Katz, A. A. (2014). Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway. <i>Journal of Molecular Signaling</i>, http://hdl.handle.net/11427/13628 | en_ZA |
| dc.identifier.chicagocitation | Adefuye, Anthonio O, Kurt J Sales, and Arieh A Katz "Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway." <i>Journal of Molecular Signaling</i> (2014) http://hdl.handle.net/11427/13628 | en_ZA |
| dc.identifier.citation | Adefuye, A. O., Sales, K. J., & Katz, A. A. (2014). Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway. Journal of molecular signaling, 9(1), 8. | |
| dc.identifier.ris | TY - Journal Article AU - Adefuye, Anthonio O AU - Sales, Kurt J AU - Katz, Arieh A AB - Abstract Background Cervical cancer is a chronic inflammatory disease of multifactorial etiology usually presenting in sexually active women. Exposure of neoplastic cervical epithelial cells to seminal plasma (SP) has been shown to promote the growth of cancer cells in vitro and tumors in vivo by inducing the expression of inflammatory mediators including pro-inflammatory cytokines. IL-1α is a pleotropic pro-inflammatory cytokine induced in several human cancers and has been associated with virulent tumor phenotype and poorer prognosis. Here we investigated the expression of IL-1α in cervical cancer, the role of SP in the regulation of IL-1α in neoplastic cervical epithelial cells and the molecular mechanism underlying this regulation. Methods and results Real-time quantitative RT-PCR confirmed the elevated expression of IL-1α mRNA in cervical squamous cell carcinoma and adenocarcinoma tissue explants, compared with normal cervix. Using immunohistochemistry, IL-1α was localized to the neoplastically transformed squamous, columnar and glandular epithelium in all cases of squamous cell carcinoma and adenocarcinomas explants studied. We found that SP induced the expression of IL-α in both normal and neoplastic cervical tissue explants. Employing HeLa (adenocarcinoma) cell line as a model system we identified PGE2 and EGF as possible ligands responsible for SP-mediated induction of IL-1α in these neoplastic cells. In addition, we showed that SP activates EP2/EGFR/PI3kinase-Akt signaling to induce IL-1α mRNA and protein expression. Furthermore, we demonstrate that in normal cervical tissue explants the induction of IL-1α by SP is via the activation of EP2/EGFR/PI3 kinase-Akt signaling. Conclusion SP-mediated induction of IL-1α in normal and neoplastic cervical epithelial cells suggests that SP may promote cervical inflammation as well as progression of cervical cancer in sexually active women. DA - 2014-08-08 DB - OpenUCT DO - 10.1186/1750-2187-9-8 DP - University of Cape Town J1 - Journal of Molecular Signaling LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway TI - Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway UR - http://hdl.handle.net/11427/13628 ER - | en_ZA |
| dc.identifier.uri | http://hdl.handle.net/11427/13628 | |
| dc.identifier.uri | http://dx.doi.org/10.1186/1750-2187-9-8 | |
| dc.identifier.vancouvercitation | Adefuye AO, Sales KJ, Katz AA. Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway. Journal of Molecular Signaling. 2014; http://hdl.handle.net/11427/13628. | en_ZA |
| dc.language.rfc3066 | en | |
| dc.publisher.department | MRC/UCT Receptor Biology Research Group | en_ZA |
| dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
| dc.publisher.institution | University of Cape Town | |
| dc.rights | This is an Open Access article distributed under the terms of the Creative Commons Attribution License | * |
| dc.rights.holder | Adefuye et al.; licensee BioMed Central Ltd. | |
| dc.rights.uri | http://creativecommons.org/licenses/by/3.0 | * |
| dc.source | Journal of Molecular Signaling | en_ZA |
| dc.source.uri | http://www.jmolecularsignaling.com | |
| dc.title | Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway | |
| dc.type | Journal Article | en_ZA |
| uct.type.filetype | ||
| uct.type.filetype | Text | |
| uct.type.filetype | Image | |
| uct.type.publication | Research | en_ZA |
| uct.type.resource | Article | en_ZA |