Universität zu Köln

De Andrea, Marco ORCID: 0000-0002-3188-5783, Ritta, Massimo, Landini, Manuela M., Borgogna, Cinzia ORCID: 0000-0001-9973-2620, Mondini, Michele ORCID: 0000-0001-5803-0083, Kern, Florian, Ehrenreiter, Karin, Baccarini, Manuela ORCID: 0000-0002-3033-391X, Marcuzzi, Gian Paolo, Smola, Sigrun, Pfister, Herbert, Landolfo, Santo and Gariglio, Marisa ORCID: 0000-0002-5187-0140 (2010). Keratinocyte-Specific Stat3 Heterozygosity Impairs Development of Skin Tumors in Human Papillomavirus 8 Transgenic Mice. Cancer Res., 70 (20). S. 7938 - 7949. PHILADELPHIA: AMER ASSOC CANCER RESEARCH. ISSN 0008-5472

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Abstract

Human papillomaviruses (HPV) of the genus beta 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 beta-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. (C) 2010 AACR.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code De Andrea, Marco UNSPECIFIED orcid.org/0000-0002-3188-5783 UNSPECIFIED Ritta, Massimo UNSPECIFIED UNSPECIFIED UNSPECIFIED Landini, Manuela M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Borgogna, Cinzia UNSPECIFIED orcid.org/0000-0001-9973-2620 UNSPECIFIED Mondini, Michele UNSPECIFIED orcid.org/0000-0001-5803-0083 UNSPECIFIED Kern, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Ehrenreiter, Karin UNSPECIFIED UNSPECIFIED UNSPECIFIED Baccarini, Manuela UNSPECIFIED orcid.org/0000-0002-3033-391X UNSPECIFIED Marcuzzi, Gian Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED Smola, Sigrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Landolfo, Santo UNSPECIFIED UNSPECIFIED UNSPECIFIED Gariglio, Marisa UNSPECIFIED orcid.org/0000-0002-5187-0140 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-494224
DOI:	10.1158/0008-5472.CAN-10-1128
Journal or Publication Title:	Cancer Res.
Volume:	70
Number:	20
Page Range:	S. 7938 - 7949
Date:	2010
Publisher:	AMER ASSOC CANCER RESEARCH
Place of Publication:	PHILADELPHIA
ISSN:	0008-5472
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIGNAL TRANSDUCER; EPIDERMODYSPLASIA-VERRUCIFORMIS; TARGETED DISRUPTION; PROMOTION STAGES; TRANSCRIPTION 3; CARCINOGENESIS; GENE; EXPRESSION; ACTIVATOR; SURVIVAL Multiple languages Oncology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49422