Alterations of the metastasis suppressor gene nm23 and the proto-oncogene c-myc in human testicular germ cell tumors.
The putative metastasis suppressor genes nm23-H1, nm23-H2 and the c-myc proto-oncogene were investigated in testicular germ cell tumors (GCTs) using Southern and Northern blotting as well as semiquantitative reverse transcription polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analysis. When studying Bgl II RFLPs, allelic losses of the nm23 gene were found in 3/12 (25%) informative tumors, and all 3 had lymph node and/or distant metastases. A 2 to 7 fold nm23 mRNA overexpression was found in 22/34 (64.7%) tumors examined. RT-PCR revealed that this phenomenon is mainly a consequence of nm23-H2 overexpression. Overexpression of both the H1 and the H2 gene was predominantly found in the seminoma subtype and was not associated with tumor stage. Only 1/25 tumors, a seminoma with distant metastases, had a point mutation in the coding region of the nm23-H2 gene as demonstrated by SSCP analysis. None of the 8 seminomas and only 1/13 non-seminomas had c-myc overexpression. No abnormalities of the c-myc gene could be detected on the DNA level. Despite the fact that in previous investigations nm23-H2 was demonstrated to be a putative transcription factor for c-myc, no coexpression of c-myc and nm23-H2 was found by quantitative RT-PCR in this study.
Schmidt
B
B
Department of Urology, Heinrich-Heine-University, Düsseldorf, Germany.
Ackermann
R
R
Hartmann
M
M
Strohmeyer
T
T
D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016259:Genes, myc / Q000235:genetics*; D018237:Germinoma / Q000235:genetics* / Q000556:secondary; D006801:Humans; D008297:Male; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D017354:Point Mutation; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000096:biosynthesis; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*
C000715470:MAS1 protein, human; D054778:NM23 Nucleoside Diphosphate Kinases; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins