| First Author | Winter M | Year | 2016 |
| Journal | Oncotarget | Volume | 7 |
| Issue | 30 | Pages | 46862-46870 |
| PubMed ID | 27409835 | Mgi Jnum | J:258722 |
| Mgi Id | MGI:6147912 | Doi | 10.18632/oncotarget.10478 |
| Citation | Winter M, et al. (2016) Deletion of 14-3-3sigma sensitizes mice to DMBA/TPA-induced papillomatosis. Oncotarget 7(30):46862-46870 |
| abstractText | The p53-inducible cell cycle regulator 14-3-3sigma exhibits tumor suppressive functions and is highly expressed in differentiating layers of the epidermis and hair follicles. 14-3-3sigma/SFN/stratifin is frequently silenced in human epithelial cancers, and experimental down-regulation of 14-3-3sigma expression immortalizes primary human keratinocytes. In the repeated-epilation (ER) mouse model, a heterozygous nonsense mutation of 14-3-3sigma causes repeated hair-loss, hyper-proliferative epidermis, and spontaneous development of papillomas and squamous cell carcinomas in aging mice. Therefore, loss of 14-3-3sigma function might contribute to epithelial tumor development. Here, we generated mice with loxP sites surrounding the single 14-3-3sigma exon which allowed Cre-mediated deletion of the gene. 14-3-3sigma-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 14-3-3sigma did not enhance spontaneous epidermal tumor development, whereas it increased the frequency and size of DMBA/TPA-induced papillomas. In conclusion, 14-3-3sigma 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 14-3-3sigma is not equivalent to loss of 14-3-3sigma, but may represent a gain-of-function variant, which does not reflect the organismal function of wild-type 14-3-3sigma. |
