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.

Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.