Universität zu Köln

Deshmukh, Jayesh, Pofahl, Ruth, Pfister, Herbert and Haase, Ingo (2016). Deletion of epidermal Rac1 inhibits HPV-8 induced skin papilloma formation and facilitates HPV-8-and UV-light induced skin carcinogenesis. Oncotarget, 7 (36). S. 57841 - 57851. ORCHARD PARK: IMPACT JOURNALS LLC. ISSN 1949-2553

Full text not available from this repository.

Abstract

Overexpression and increased activity of the small Rho GTPase Rac1 has been linked to squamous cell carcinoma of the epidermis and mucosa in humans. Targeted deletion of Rac1 or inhibition of Rac1 activity in epidermal keratinocytes reduced papilloma formation in a chemical skin carcinogenesis mouse model. However, a potential role of Rac1 in HPV- and UV-light induced skin carcinogenesis has not been investigated so far, solar UV radiation being an important carcinogen to the skin. To investigate this, we deleted Rac1 or modulated its activity in mice with transgenic expression of Human papilloma virus type-8 (HPV-8) in epidermal keratinocytes. Our data show that inhibition or deletion of Rac1 results in reduced papilloma formation upon UV-irradiation with a single dose, whereas constitutive activation of Rac1 strongly increases papilloma frequency in these mice. Surprisingly, we observed that, upon chronic UV-irradiation, the majority of mice with transgenic expression of HPV-8 and epidermis specific Rac1 deletion developed squamous cell carcinomas. Taken together, our data show that Rac1 exerts a dual role in skin carcinogenesis: its activation is, on one hand, required for HPV-8- and UV-light induced papilloma formation but, on the other, suppresses the development of squamous cell carcinomas.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Deshmukh, Jayesh UNSPECIFIED UNSPECIFIED UNSPECIFIED Pofahl, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Herbert UNSPECIFIED UNSPECIFIED UNSPECIFIED Haase, Ingo UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-262556
DOI:	10.18632/oncotarget.11069
Journal or Publication Title:	Oncotarget
Volume:	7
Number:	36
Page Range:	S. 57841 - 57851
Date:	2016
Publisher:	IMPACT JOURNALS LLC
Place of Publication:	ORCHARD PARK
ISSN:	1949-2553
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DNA-DAMAGE FOCI; ULTRAVIOLET-RADIATION; HAIR FOLLICLE; GTPASE; CARCINOMAS; SENESCENCE; DEFICIENT; REPAIR; MOUSE; CELLS Multiple languages Oncology; Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26255