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Epidermal abnormalities and increased malignancy of skin tumors in human epidermal keratin 8‐expressing transgenic mice
Author(s) -
Casanova M. Llanos,
Bravo Ana,
MartínezPalacio Jesús,
Jesús FernándezAceñero M.,
Villanueva Concepción,
Larcher Fernando,
Conti Claudio J.,
Jorcano José L.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-1683fje
Subject(s) - keratin , keratin 5 , keratin 8 , carcinogenesis , epidermis (zoology) , biology , keratin 14 , pathology , malignancy , malignant transformation , genetically modified mouse , cancer research , cancer , neoplastic transformation , skin cancer , transgene , medicine , anatomy , genetics , gene
Keratins K8 and K18 are the major components of the intermediate filament cytoskeleton of simple epithelia. Increased levels of these keratins have been associated with invasive growth and progression to malignancy in different types of human and murine epithelial tumors (including skin tumors), and even in tumors from nonepithelial origin. However, it has not yet clarified whether K8/K18 expression in tumors is cause or consequence of malignancy. Given the increasing incidence of epidermal cancer in humans (40% of all tumors diagnosed), we generated a mouse model to examine the role of simple epithelium keratins in the establishment and progression of human skin cancer. Transgenic mice expressing human K8 in the epidermis showed severe epidermal and hair follicle dysplasia with concomitant alteration in epidermal differentiation markers. The severity of the skin phenotype of these transgenic mice increases with age, leading to areas of preneoplastic transformation. Skin carcinogenesis assays showed a dramatic increase in the progression of papillomas toward malignancy in transgenic animals. These results support the idea that K8 alters the epidermal cell differentiation, favors the neoplastic transformation of cells, and is ultimately responsible of the invasive behavior of transformed epidermal cells leading of conversion of benign to malignant tumors.