Inverse relationship between p53 and phospho-Chk1 (Ser317) protein expression in UVB-induced skin tumors in SKH-1 mice
| Autor: | Qing Yun Peng, Allan H. Conney, Jamie J. Bernard, Tao Li, Yao Ping Lu, You Rong Lou |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Skin Neoplasms
animal structures Ultraviolet Rays Blotting Western Clinical Biochemistry Cell Biology environment and public health Article Pathology and Forensic Medicine Mice Basal (phylogenetics) Serine medicine Animals CHEK1 Phosphorylation Molecular Biology Mice Knockout Mice Hairless integumentary system Molecular biology Hairless enzymes and coenzymes (carbohydrates) medicine.anatomical_structure Checkpoint Kinase 1 Knockout mouse Carcinoma Squamous Cell Cancer research Immunohistochemistry Female Tumor Suppressor Protein p53 biological phenomena cell phenomena and immunity Protein Kinases Immunostaining |
| Zdroj: | Experimental and Molecular Pathology. 96:126-131 |
| ISSN: | 0014-4800 |
| DOI: | 10.1016/j.yexmp.2013.10.011 |
| Popis: | Immunohistochemical evaluation of serial stored paraffin sections from 42 keratoacanthomas and 11 squamous cell carcinomas demonstrated that skin tumors from UVB-exposed mice showed an inverse relationship (>95%) between p53 protein expression and phospho-Chk1 (Ser317), but not phospho-Chk1 (Ser345) protein expression. Tumors expressing high levels and large areas of p53 protein had no detectable phospho-Chk1 (Ser317), whereas tumors expressing high levels and large areas of phospho-Chk1 (Ser317) protein had no detectable p53. Squamous cell carcinomas that demonstrated heterogeneous p53 and phospho-Chk1 (Ser317) protein expression within the same tumor showed that areas expressing p53 were negative for phospho-Chk1 (Ser317) immunostaining while areas expressing phospho-Chk1 (Ser317) were negative for p53. Similar patterns were observed for keratoacanthomas. These findings were also observed in epidermal areas distant from tumors that demonstrated no detectable phospho-Chk1 (Ser317), but appreciable p53 protein in the basal layer. Tumors from congenic hairless p53 knockout mice had elevated levels of phospho-Chk1 (Ser317) compared to tumors from p53 wild-type SKH-1 controls. After a single exposure to UVB, normal epidermal cells from a p53 knockout mouse expressed a relatively high level of phospho-Chk1 (Ser317) where as epidermal cells from a p53wild-type littermate induced p53 protein and expressed a relatively low level of phospho-Chk1 (Ser317). These data illustrate the dynamic regulation of checkpoint function, suggesting that phosphorylation of Chk1 on Serine 317 is regulated by p53 status and that p53 may act as a molecular on/off switch for phosphorylation at this site. |
| Databáze: | OpenAIRE |
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