| First Author | Devos M | Year | 2017 |
| Journal | J Invest Dermatol | Volume | 137 |
| Issue | 2 | Pages | 494-505 |
| PubMed ID | 27725202 | Mgi Jnum | J:240056 |
| Mgi Id | MGI:5882272 | Doi | 10.1016/j.jid.2016.09.026 |
| Citation | Devos M, et al. (2017) Elevated DeltaNp63alpha Levels Facilitate Epidermal and Biliary Oncogenic Transformation. J Invest Dermatol 137(2):494-505 |
| abstractText | Unlike its family member p53, TP63 is rarely mutated in human cancer. However, DeltaNp63alpha protein levels are often elevated in tumors of epithelial origin, such as squamous cell carcinoma and cholangiocarcinoma. To study the oncogenic properties of DeltaNp63alpha in vivo, we generated transgenic mice overexpressing DeltaNp63alpha from the Rosa26 locus promoter controlled by keratin 5-Cre. We found that these mice spontaneously develop epidermal cysts and ectopic DeltaNp63alpha expression in the bile duct epithelium that leads to dilatation of the intrahepatic biliary ducts, to hepatic cyst formation and bile duct adenoma. Moreover, when subjected to models of 7,12-dimethylbenz[a]anthracene-based carcinogenesis, tumor initiation was increased in DeltaNp63alpha transgenic mice in a gene dosage-dependent manner although DeltaNp63alpha overexpression did not alter the sensitivity to 7,12-dimethylbenz[a]anthracene-induced cytotoxicity in vivo. However, keratinocytes isolated from DeltaNp63alpha transgenic mice displayed increased survival and delayed cellular senescence compared with wild-type keratinocytes, marked by decreased p16Ink4a and p19Arf expression. Taken together, we show that increased DeltaNp63alpha protein levels facilitate oncogenic transformation in the epidermis as well as in the bile duct. |
