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Exp Mol Pathol. 2014 Feb;96(1):126-31. doi: 10.1016/j.yexmp.2013.10.011. Epub 2013 Oct 30.

Inverse relationship between p53 and phospho-Chk1 (Ser317) protein expression in UVB-induced skin tumors in SKH-1 mice.

Author information

1
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States.
2
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, United States. Electronic address: yaoping.lu@pharmacy.rutgers.edu.

Abstract

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) whereas epidermal cells from a p53 wild-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.

KEYWORDS:

Cancer; Phospho-chk1; Skin; Tumor; UVB; p53

PMID:
24184701
PMCID:
PMC4365929
DOI:
10.1016/j.yexmp.2013.10.011
[Indexed for MEDLINE]
Free PMC Article

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