RT Journal Article
T1 Increased IKK alpha Expression in the Basal Layer of the Epidermis of Transgenic Mice Enhances the Malignant Potential of Skin Tumors
A1 Alameda, Josefa P.
A1 Moreno Maldonado, Rodolfo
A1 Fernández Aceñero, María Jesús
A1 Navarro, Manuel
A1 Page, Angustias
A1 Jorcano, José L.
A1 Bravo Moral, Ana María
A1 Ramírez, Ángel
A1 Llanos Casanova, M.
K1 Skin tumors
K1 Epidermis
K1 Keratinocytes
K1 Carcinogenesis
K1 Mouse models
K1 Benign tumors
K1 Transcription factors
K1 Malignant tumors
AB Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKα expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKα in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKα transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-α6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKα-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKα in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-α6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKα skin tumors.
PB PLOS
YR 2011
FD 2011
LK http://hdl.handle.net/10347/22320
UL http://hdl.handle.net/10347/22320
LA eng
NO Alameda, J. P., Moreno-Maldonado, R., Fernandez-Acenero, M. J., Navarro, M., Page, A., Jorcano, J. L., ... & Casanova, M. L. (2011). Increased IKKα expression in the basal layer of the epidermis of transgenic mice enhances the malignant potential of skin tumors. PLoS One, 6(7): e21984. https://doi.org/10.1371/journal.pone.0021984
NO This work was funded by grants from the Ministerio de Ciencia e Innovación (PI10/01480, SAF2010-22156) to MLC and AR respectively
DS Minerva
RD 25 abr 2026