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BioMed Research International
Volume 2017, Article ID 7868645, 9 pages
https://doi.org/10.1155/2017/7868645
Research Article

The PDZ-Binding Motif of HPV16-E6 Oncoprotein Modulates the Keratinization and Stemness Transcriptional Profile In Vivo

1Genetics and Cancer Research Unit, Hospital Juárez de México (HJM), 07760 Mexico City, Mexico
2Oncogenomic Department, Instituto Nacional de Medicina Genómica (INMEGEN), 14610 Mexico City, Mexico
3Laboratory of Cell and Developmental Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD 21702, USA
4Department of Cellular Biology, Centro de Investigación y de Estudios Avanzados (Cinvestav), 07360 Mexico City, Mexico
5Department of Physiology, Biophysics, and Neurosciences, Centro de Investigación y de Estudios Avanzados (Cinvestav), 07360 Mexico City, Mexico
6Laboratory of Clinic Research, Unidad Académica de Ciencias Químico-Biológicas, Universidad Autónoma de Guerrero (UAGro), 39070 Chilpancingo de los Bravo, GRO, Mexico
7Department of Genetics and Molecular Biology, Centro de Investigación y de Estudios Avanzados (Cinvestav), 07360 Mexico City, Mexico

Correspondence should be addressed to Patricio Gariglio; xm.vatsevnic@ladiv and José Bonilla-Delgado; xm.vatsevnic@allinobj

Received 9 March 2017; Revised 24 July 2017; Accepted 24 August 2017; Published 10 October 2017

Academic Editor: Henry Wong

Copyright © 2017 Enoc Mariano Cortés-Malagón et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective. The aim of this work was to compare the early gene expression profiles in the skin of HPV16-E6 transgenic mice regulated by the E6 PDZ-binding motif. Materials and Methods. The global transcriptional profiles in dorsal skin biopsies from K14E6 and K14E6Δ146-151 transgenic mice were compared using microarrays. Relevant genes obtained from the most differentially expressed processes were further examined by RT-qPCR, in situ RT-PCR, Western blot, or immunofluorescence. Results. The transcriptomic landscape of K14E6 versus K14E6Δ146-151 shows that the most affected expression profiles were those related to keratinocyte differentiation, stem cell maintenance, and keratinization. Additionally, downregulation of epidermal stemness markers such as K15 and CD34, as well as the upregulation of cytokeratin 6b, appeared to be dependent on the E6 PDZ-binding motif. Finally, wound healing, a physiological process linked to stemness, is impaired in the K14E6 mice compared to K14E6Δ146-151. Conclusion. The E6 PDZ-binding motif appears to affect stemness and keratinization during early stages of skin carcinogenesis. As E6 plays a significant role in HPV-induced skin carcinogenesis, the K14E6 versus K14E6Δ146-151 transcriptional profile provides a source of valuable data to uncover novel E6 functions in the skin.