Priority Research Papers:

Deletion of 14-3-3σ sensitizes mice to DMBA/TPA-induced papillomatosis

Markus Winter, Dmitri Lodygin, Berlinda Verdoodt and Heiko Hermeking _

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Oncotarget. 2016; 7:46862-46870. https://doi.org/10.18632/oncotarget.10478

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Markus Winter1, Dmitri Lodygin2, Berlinda Verdoodt3 and Heiko Hermeking1,4,5

1 Experimental and Molecular Pathology, Institute of Pathology, Ludwig-Maximilians-Universität München, Munich, Germany

2 Institute of Neuroimmunology and Institute for Multiple Sclerosis Research, University Medical Center Göttingen, Göttingen, Germany

3 Institute of Pathology, Ruhr-University Bochum, Bochum, Germany

4 German Cancer Consortium (DKTK), Heidelberg, Germany

5 German Cancer Research Center (DKFZ), Heidelberg, Germany

Correspondence to:

Heiko Hermeking, email:

Keywords: 14-3-3sigma knock-out mouse, skin carcinogenesis, repeated epilation/ER

Received: May 23, 2016 Accepted: June 25, 2016 Published: July 07, 2016


The p53-inducible cell cycle regulator 14-3-3σ exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3σ/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3σ expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3σ causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3σ function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3σ exon which allowed Cre-mediated deletion of the gene. 14-3-3σ-deficient mice are viable, but demonstrate a permanently disheveled fur. However, histological analyses of the skin did not reveal obvious defects in the hair follicles or the epidermis. Deletion of 14-3-3σ did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3σ is dispensable for normal epidermal homeostasis but critical for suppression of chemically-induced skin carcinogenesis. In addition, these results suggest that the ER mutation of 14-3-3σ is not equivalent to loss of 14-3-3σ, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3σ.

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