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Increased expression of cellular RNA-binding proteins in HPV-induced neoplasia and cervical cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
2009 (English)In: Journal of Medical Virology, ISSN 0146-6615, E-ISSN 1096-9071, Vol. 81, no 5, 897-907 p.Article in journal (Refereed) Published
Abstract [en]

The expression profile of a panel of RNA-binding proteins (heterogeneous ribonucleoprotein (hnRNP) A1, hnRNP C1/C2, hnRNP H, hnRNP I, ASF/SF2, SR proteins, HuR and U2AF(65)) and markers of differentiation, proliferation and neoplasia (cytokeratin (CK) 13, CK-14, proliferating cell nuclear antigen (PCNA), Syndecan-1 and p16INK4a) were analyzed in 50 formalin fixed paraffin embedded cervical tissues using immunohistochemistry. The samples included histologically normal cervical epithelium, human papillomavirus (HPV) induced low-grade and high-grade pre-malignant lesions and cervical cancers. All samples were tested for HPV DNA using nested PCR. Forty-nine of the 50 tissue samples tested positive for HPV, 27 tissue samples (54%) were HPV-16 positive and 4 samples (8%) were HPV-18 positive. The immunohistochemistry results detected different expression levels of the various proteins in basal epithelial cells in histologically normal epithelium followed by an increase in expression in the intermediate layers, whereas the superficial layers remained negative for all tested RNA-binding proteins. Expression of all RNA-binding proteins increased in neoplastic lesions and highest expression was detected in cervical cancers. p16INK4a had a stronger association with high-grade lesions when compared with the RNA-binding proteins. The expression profile of the RNA-binding proteins is similar to PCNA expression in histologically normal epithelium as well as in lesions (low-grade and high-grade) and cervical cancers. As PCNA expression has been suggested to mimic HPV E6/E7 expression in cervical epithelium, the results suggest the RNA-binding protein analyzed here regulate HPV early gene expression directly and late gene expression indirectly.

Place, publisher, year, edition, pages
2009. Vol. 81, no 5, 897-907 p.
Keyword [en]
splicing, p16INK4a, hnRNP A1, ASF/SF2, PTB, hnRNP C1/C2, hnRNP H, HuR, hnRNP I, U2AF65, SR proteins, HPV-16, papillomavirus
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-119532DOI: 10.1002/jmv.21406ISI: 000264906800018PubMedID: 19319956OAI: oai:DiVA.org:uu-119532DiVA: diva2:300395
Available from: 2010-02-26 Created: 2010-02-26 Last updated: 2010-08-03Bibliographically approved

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