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To study its contribution to tumor development, we overexpressed the mutant or wild-type (WT) human \u03b21 subunit in the basal layer of mouse epidermis using the keratin 14 promoter. The transgenic integrins were expressed at the cell surface and were functional, with the T188I\u03b21 subunit promoting cell spreading to a greater extent than WT\u03b21. Epidermal proliferation and differentiation were unaffected and no expansion of the stem cell compartment was detected. During chemical carcinogenesis, both transgenes increased papilloma formation, but only the T188I\u03b21 transgene stimulated the conversion of papillomas to SCCs. Papillomas bearing the mutation showed increased Erk activity and reduced differentiation. SCCs expressing T188I\u03b21 were less well-differentiated than those expressing WT\u03b21. These observations establish that the expression of a genetic variant in the I-like domain of \u03b21 integrins does not affect normal epidermal homeostasis, but increases tumor susceptibility and influences tumor type. [Cancer Res 2009;69(4):1334\u201342]<\/jats:p>","DOI":"10.1158\/0008-5472.can-08-3051","type":"journal-article","created":{"date-parts":[[2009,2,3]],"date-time":"2009-02-03T23:04:00Z","timestamp":1233702240000},"page":"1334-1342","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["An Activating \u03b21 Integrin Mutation Increases the Conversion of Benign to Malignant Skin Tumors"],"prefix":"10.1158","volume":"69","author":[{"given":"Manuela","family":"Ferreira","sequence":"first","affiliation":[{"name":"1Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom;"},{"name":"2Ph.D. Programme in Experimental Biology and Biomedicine, Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; and"}]},{"given":"Hironobu","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"1Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom;"}]},{"given":"Kazumasa","family":"Morita","sequence":"additional","affiliation":[{"name":"3Department of Dermatology, Tenri Yorozu Hospital, Tenri, Japan"}]},{"given":"Fiona M.","family":"Watt","sequence":"additional","affiliation":[{"name":"1Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom;"}]}],"member":"1086","published-online":{"date-parts":[[2009,2,12]]},"reference":[{"key":"2022061701333600800_B1","doi-asserted-by":"crossref","unstructured":"Watt FM. 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