Universität zu Köln

Donmez, Hanife Guler, Akgor, Utku, Onder, Sevgen, Tanacan, Atakan, Kuru, Oguzhan ORCID: 0000-0002-4497-7222, Ozgul, Nejat, Usubutun, Alp, Hufbauer, Martin ORCID: 0000-0003-4106-0520, Akgul, Baki and Beksac, Mehmet Sinan . Impact of Human Papillomavirus on Wnt/Beta-Catenin Signaling in Morphological Inconspicuous Cervicovaginal Cells. Acta Cytol.. BASEL: KARGER. ISSN 1938-2650

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Abstract

Introduction: The aim of this study was to identify early changes in the Wnt/beta-catenin signaling pathway in high-risk human papillomavirus (HPV) infected cervicovaginal cells and to correlate these changes with cell proliferation, apoptosis, and autophagic processes. Methods: We evaluated 91 cervicovaginal smears of women with (n = 41) and without (n = 50) HPV-DNA. Smears were stained against beta-catenin, c-myc, secreted frizzled-related protein 4 (sFRP4), cleaved caspase-3, and the autophagy markers Beclin-1 and light chain 3B. In addition, sFRP-1, -2, -3, -4, -5 mRNA levels were determined by quantitative reverse transcription-PCR in primary keratinocytes and FaDu cells expressing HPV16-E6, -E7, or -E6E7. Results: Our data indicated that the Wnt/beta-catenin signaling is activated in HPV (+) cervicovaginal cells that can already be detected in cells with no obvious changes in cellular morphology (HPV [+]/cyto [-]). These cells also had significantly higher sFRP4 levels when compared to HPV-negative samples. In primary keratinocytes, sFRP4 was found to be absent and sFRP1 and sFRP2 to be repressed in the presence of HPV16-E6 and E7. Interestingly, sFRP4 is expressed in FaDu cells and can be upregulated in the presence of E6E7. Curiously, SFRP4 expression correlated with an increase in the level of autophagic markers in HPV (+)/cyto (-) smears. Conclusion: In conclusion, the activation of the Wnt/beta-catenin signaling pathway and upregulation of sFRP4, paralleled by an activation of the autophagic pathway may represent predisposing cellular factors early after HPV infection which need to be further determined in larger study.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Donmez, Hanife Guler UNSPECIFIED UNSPECIFIED UNSPECIFIED Akgor, Utku UNSPECIFIED UNSPECIFIED UNSPECIFIED Onder, Sevgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Tanacan, Atakan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuru, Oguzhan UNSPECIFIED orcid.org/0000-0002-4497-7222 UNSPECIFIED Ozgul, Nejat UNSPECIFIED UNSPECIFIED UNSPECIFIED Usubutun, Alp UNSPECIFIED UNSPECIFIED UNSPECIFIED Hufbauer, Martin UNSPECIFIED orcid.org/0000-0003-4106-0520 UNSPECIFIED Akgul, Baki UNSPECIFIED UNSPECIFIED UNSPECIFIED Beksac, Mehmet Sinan UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-683813
DOI:	10.1159/000522635
Journal or Publication Title:	Acta Cytol.
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1938-2650
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CERVICAL-CANCER; E6 ONCOPROTEIN; BETA-CATENIN; PAP TEST; HPV; EXPRESSION; AUTOPHAGY; PROTEIN; METHYLATION; INFECTION Multiple languages Pathology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/68381