Germ cell tumors of the testis overexpress wild-type p53

Details

Serval ID
serval:BIB_641F54AB0D86
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Germ cell tumors of the testis overexpress wild-type p53
Journal
American Journal of Pathology
Author(s)
Guillou  L., Estreicher  A., Chaubert  P., Hurlimann  J., Kurt  A. M., Metthez  G., Iggo  R., Gray  A. C., Jichlinski  P., Leisinger  H. J., Benhattar  J.
ISSN
0002-9440
Publication state
Published
Issued date
10/1996
Peer-reviewed
Oui
Volume
149
Number
4
Pages
1221-1228
Notes
Journal Article Research Support, Non-U.S. Gov't --- Old month value: Oct
Abstract
Several recent studies have suggested that testicular germ cell tumors express high levels of wild-type p53 protein. To clarify and confirm this unexpected result, we have investigated seminomatous and nonseminomatous germ cell tumors at the genomic, mRNA, and protein levels. Thirty-five tumors were examined for p53 overexpression using antibodies directed against the p53 (PAb1801, PAb240, and CM1), mdm2 (IF2), and p21Waf1/Clp1 (EA10) proteins. Thirty-two tumors were screened for p53 mutations by single-strand conformation polymorphism analysis. Eighteen tumors were screened with a functional assay that tests the transcriptional competence of human p53 protein expressed in yeast. On frozen sections, 100, 65, 35, 73, and 0% of tumors reacted with the CM1, PAb240, PAb1801, IF2, and EA10 antibodies, respectively. No p53 mutations were detected by single-strand conformation polymorphism or by functional assay. The fact that many tumors overexpress wild-type p53 but not mdm2 rules out mdm2 overexpression as a general explanation for the presence of wild-type p53 in these tumors. The absence of p21 overexpression suggests that p53 may be unable to activate transcription of critical target genes, which may explain why the presence of wild-type p53 is tolerated in this tumor type, although the mechanism for this transcriptional inactivity remains to be established.
Keywords
Cyclin-Dependent Kinase Inhibitor p21 Cyclins/metabolism DNA Mutational Analysis DNA, Neoplasm/genetics Germinoma/genetics/*metabolism/pathology Humans Male Testicular Neoplasms/genetics/*metabolism/pathology Transfection Tumor Suppressor Protein p53/genetics/*metabolism Yeasts/genetics
Pubmed
Web of science
Create date
21/01/2008 16:10
Last modification date
20/08/2019 14:20
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