Basal Cell Carcinoma and Its Development

Cancer Research - Tập 64 Số 3 - Trang 934-941 - 2004
Mariateresa Mancuso1, Simonetta Pazzaglia2, Mirella Tanori2, Heidi Hahn3, Paola Merola2, Simonetta Rebessi2, Michael J. Atkinson4, Vincenzo Di Majo2, Vincenzo Covelli5, Anna Saran2
1Biotechnology Unit and Radiation Protection Unit, ENEA-Ente per le Nuove Tecnologie, l'Energia e l'Ambiente, Centro Ricerche, Casaccia, Rome, Italy.
21Biotechnology Unit and
33Institute of Human Genetics, University of Goettingen, Goettingen, Germany; and
44Institute of Pathology, GSF-National Research Center for Environment and Health, Munich, Germany
52Radiation Protection Unit, ENEA-Ente per le Nuove Tecnologie, l’Energia e l’Ambiente, Centro Ricerche, Casaccia, Rome, Italy;

Tóm tắt

Abstract Loss-of-function mutations in Patched (Ptch1) are implicated in constitutive activation of the Sonic hedgehog pathway in human basal cell carcinomas (BCCs), and inherited Ptch1 mutations underlie basal cell nevus syndrome in which a typical feature is multiple BCC occurring with greater incidence in portals of radiotherapy. Mice in which one copy of Ptch1 is inactivated show increased susceptibility to spontaneous tumor development and hypersensitivity to radiation-induced tumorigenesis, providing an ideal in vivo model to study the typical pathologies associated with basal cell nevus syndrome. We therefore examined BCC development in control and irradiated Ptch1neo67/+ mice. We show that unirradiated mice develop putative BCC precursor lesions, i.e., basaloid hyperproliferation areas arising from both follicular and interfollicular epithelium, and that these lesions progress to nodular and infiltrative BCCs only in irradiated mice. Data of BCC incidence, multiplicity, and latency support the notion of epidermal hyperproliferations, nodular and infiltrative BCC-like tumors representing different stages of tumor development. This is additionally supported by the pattern of p53 protein expression observed in BCC subtypes and by the finding of retention of the normal remaining Ptch1 allele in all nodular, circumscribed BCCs analyzed compared with its constant loss in infiltrative BCCs. Our data suggest chronological tumor progression from basaloid hyperproliferations to nodular and then infiltrative BCC occurring in a stepwise fashion through the accumulation of sequential genetic alterations.

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Cancer Research

Tập 64 Số 3

934-941

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