Keratinocyte-specific stat3 heterozygosity impairs development of skin tumors in human papillomavirus 8 transgenic mice tumors in human papillomavirus 8 transgenic mice.

Autor(en)

Marco De Andrea, Massimo Rittà, Manuela M. Landini, Cinzia Borgogna, Michele Mondini, Florian Kern, Karin Ehrenreiter, Manuela Baccarini, Gian Paolo Marcuzzi, Sigrun Smola, Herbert Pfister, Santo Landolfo, Marissa Gariglio

Abstrakt

Human papillomaviruses (HPV) of the genus β are thought to play a role in human skin cancers, but this has been difficult to establish using epidemiologic approaches. To gain insight into the transforming activities of β-HPV, transgenic mouse models have been generated that develop skin tumors. Recent evidence suggests a central role of signal transducer and activator of transcription 3 (Stat3) as a transcriptional node for cancer cell–autonomous initiation of a tumor-promoting gene signature associated with cell proliferation, cell survival, and angiogenesis. Moreover, high levels of phospho-Stat3 have been detected in tumors arising in HPV8-CER transgenic mice. In this study, we investigate the in vivo role of Stat3 in HPV8-induced skin carcinogenesis by combining our established experimental model of HPV8-induced skin cancer with epidermis-restricted Stat3 ablation. Stat3 heterozygous epidermis was less prone to tumorigenesis than wild-type epidermis. Three of the 23 (13%) Stat3+/−:HPV8 animals developed tumors within 12 weeks of life, whereas 54.3% of Stat3+/+:HPV8 mice already exhibited tumors in the same observation period (median age for tumor appearance, 10 weeks). The few tumors that arose in the Stat3+/−:HPV8 mice were benign and never progressed to a more malignant phenotype. Collectively, these results offer direct evidence of a critical role for Stat3 in HPV8-driven epithelial carcinogenesis. Our findings imply that targeting Stat3 activity in keratinocytes may be a viable strategy to prevent and treat HPV-induced skin cancer. Cancer Res; 70(20); 7938–48. ©2010 AACR.

Organisation(en)

Department für Mikrobiologie, Immunbiologie und Genetik

Externe Organisation(en)

Università Del Piemonte Orientale, Università degli Studi di Torino, Universität zu Köln

Journal

Cancer Research

Band

70

Seiten

7938-7948

Anzahl der Seiten

10

ISSN

0008-5472

DOI

https://doi.org/10.1158/0008-5472.CAN-10-1128

Publikationsdatum

2010

Peer-reviewed

Ja

ÖFOS 2012

106002 Biochemie, 106013 Genetik, 106023 Molekularbiologie, 301114 Zellbiologie

Sustainable Development Goals

SDG 3 – Gesundheit und Wohlergehen

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/keratinocytespecific-stat3-heterozygosity-impairs-development-of-skin-tumors-in-human-papillomavirus-8-transgenic-mice-tumors-in-human-papillomavirus-8-transgenic-mice(aaaf2633-193e-4e91-b5f2-4a71914de1e5).html