AKT and PERP Show Higher Expression in Precancerous than in Malignant Skin Neoplasms: Profiling in an Animal Model of Sequential Skin Carcinogenesis

Author:

Vairaktari Efstathia1ORCID,Schramm Alexander23ORCID,Vairaktari Georgia1,Derka Spyridoula1,Wilde Frank23,Sakkas Andreas23,Yapijakis Christos4ORCID,Kouri Maria5,Balakas Athanasios1,Lazaris Andreas6ORCID,Ebeling Marcel23,Vassiliou Stavros1

Affiliation:

1. Department of Oral and Maxillofacial Surgery, University General Hospital Attikon, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

2. Department of Oral and Maxillofacial Surgery, University Hospital Ulm, Albert-Einstein-Allee 10, 89081 Ulm, Germany

3. Department of Oral and Plastic Maxillofacial Surgery, Military Hospital Ulm, Academic Hospital of the University of Ulm, Oberer Eselsberg 40, 89081 Ulm, Germany

4. Unit of Orofacial Genetics, University Research Institute for the Study of Genetic and Malignant Disorders in Childhood, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

5. Department of Oral Medicine & Pathology and Hospital Dentistry, School of Dentistry, National and Kapodistrian University of Athens, 11527 Athens, Greece

6. Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece

Abstract

The primary aim of this study was to evaluate the activation of the PERP and Akt oncogenes in the induction of skin cancer in FVB/N mice by a stepwise chemical process. Forty four-week-old female FVB/N mice were randomly divided into a control group (n = 8) and two experimental groups (group A: n = 16, group B: n = 16). In the study, the groups were subjected to a two-stage carcinogenesis procedure. This consisted of an initial application of 97.4 nmol DMBA to shaved skin on the back, followed by applications of 32.4 nmol TPA after thirteen weeks for group A and after twenty weeks for group B. The control group received no treatment. Skin conditions were monitored weekly for tumor development. At the end of the experiment, the animals were euthanized for further tissue sampling. Examination of the skin lesions in the experimental groups showed a correlation with tumor progression, ranging from dysplasia to carcinoma. Tumor samples were examined both histologically and immunohistochemically. Notably, and PERP expression was higher in precancerous than in malignant tumors. The differences in expression between precancerous and benign tumors provide further evidence of a role for PERP and Akt in the transition from benign to malignant states. Our findings underscore the critical roles of PERP and Akt in the pathogenesis of skin cancer and suggest their potential as biomarkers for early detection and targets for therapeutic intervention.

Publisher

MDPI AG

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