RGD Reference Report - Chk2 tumour suppressor protein in human spermatogenesis and testicular germ-cell tumours. - Rat Genome Database

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Chk2 tumour suppressor protein in human spermatogenesis and testicular germ-cell tumours.

Authors: Bartkova, J  Falck, J  Rajpert-De Meyts, E  Skakkebaek, NE  Lukas, J  Bartek, J 
Citation: Bartkova J, etal., Oncogene. 2001 Sep 13;20(41):5897-902.
RGD ID: 2298484
Pubmed: PMID:11593395   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.onc.1204746   (Journal Full-text)

Chk2 is a transducer of DNA damage signals and a tumour suppressor whose germ-line mutations predispose to diverse tumour types. Unlike its downstream targets such as the p53 tumour suppressor, the expression patterns of Chk2 in tissues and tumours remain unknown. As DNA breaks occur commonly during gametogenesis, and p53 is wild-type and overexpressed in testicular cancer, we examined abundance and localisation of the Chk2 protein during normal development of human testes, and at various stages of germ-cell tumour (GCT) pathogenesis. Our results show that Chk2 is abundant in foetal germ cells and adult spermatogonia, yet only weakly expressed or lacking during the meiotic and later stages of spermatogenesis. High levels of Chk2 are detected in the majority of GCTs including all pre-invasive carcinoma-in-situ lesions, contrary to variable expression and even lack of Chk2 in subsets of invasive GCTs and some teratoma structures, respectively. Together with our analyses of cell culture models, these results indicate that downmodulation or lack of Chk2 is not simply attributable to quiescence or differentiation, they suggest a role for Chk2 in mitotic rather than meiotic divisions, support the concept of foetal origin of GCTs, and have implications for protein-based screening for tumour-associated aberrations of Chk2.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
embryonal carcinoma  IEP 2298484protein:decreased expression:testisRGD 
embryonal carcinoma  ISOCHEK2 (Homo sapiens)2298484; 2298484protein:decreased expression:testisRGD 
seminoma  IEP 2298484protein:decreased expression:testisRGD 
seminoma  ISOCHEK2 (Homo sapiens)2298484; 2298484protein:decreased expression:testisRGD 

Objects Annotated

Genes (Rattus norvegicus)
Chek2  (checkpoint kinase 2)

Genes (Mus musculus)
Chek2  (checkpoint kinase 2)

Genes (Homo sapiens)
CHEK2  (checkpoint kinase 2)


Additional Information