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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. J Mol Signal. 2014;9:8doi: 10.1186/1750-2187-9-8.
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, 98. https://doi.org/10.1186/1750-2187-9-8
Adefuye, Anthonio O, et al. "Seminal plasma induces the expression of IL-1α in normal and neoplastic cervical cells via EP2/EGFR/PI3K/AKT pathway." Journal of molecular signaling vol. 9 (2014): 8. doi: https://doi.org/10.1186/1750-2187-9-8
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. J Mol Signal. 2014 Aug 08;9:8. doi: 10.1186/1750-2187-9-8. eCollection 2014. PMID: 25237386; PMCID: PMC4166412.
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J Mol Signal. 2014 Aug 08;9:8. doi: 10.1186/1750-2187-9-8. eCollection 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

Anthonio O Adefuye, Kurt J Sales, Arieh A Katz

Affiliations

  1. MRC/UCT Receptor Biology Unit, Institute of Infectious Disease and Molecular Medicine and Division of Medical Biochemistry, University of Cape Town, Faculty of Health Sciences, Private bag X3 Observatory 7935, Cape Town 7925, South Africa.

PMID: 25237386 PMCID: PMC4166412 DOI: 10.1186/1750-2187-9-8

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.

Keywords: Cervical cancer; EP2/EGFR/PI3kinase-Akt signaling pathways; Interleukin-1 alpha; Seminal plasma

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