Expression changes of the MAD mitotic checkpoint gene family in renal cell carcinomas characterized by numerical chromosome changes.
Papillary and chromophobe renal cell carcinomas are characterized by multiple trisomies and monosomies, respectively, but the molecular mechanisms behind the acquisition of these numerical chromosome changes are unknown. To evaluate the role of mitotic checkpoint defects for the karyotypic patterns characteristic of these two renal cell cancer subtypes, we analyzed the messenger RNA expression levels of the major mitotic checkpoint genes of the budding uninhibited by benzimidazole family (BUB1, BUBR1, BUB3) and of the mitotic arrest deficiency family (MAD1, MAD2L1, MAD2L2) by real-time quantitative polymerase chain reaction in 30 renal cell cancer samples (11 chromophobe and 19 papillary) and 36 normal kidney tissue samples. MAD1, MAD2L1, and MAD2L2 showed significant expression differences in tumor tissue compared to controls. Chromophobe tumors presented underexpression of MAD1, and MAD2L2, whereas papillary tumors showed overexpression of MAD2L1. The expression level of the BUB gene family did not differ significantly from that of normal kidney. We conclude that expression changes in mitotic arrest deficiency genes (MAD1, MAD2L1, and MAD2L2) play a role in renal carcinogenesis characterized by multiple numerical chromosome abnormalities.
Pinto
Mafalda
M
Department of Genetics, Portuguese Oncology Institute, Rua Dr António Bernardino de Almeida, 4200-072,, Porto, Portugal.
Soares
Maria J
MJ
Cerveira
Nuno
N
Henrique
Rui
R
Ribeiro
Franclim R
FR
Oliveira
Jorge
J
Jerónimo
Carmen
C
Teixeira
Manuel R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000235:genetics; D002291:Carcinoma, Papillary / Q000235:genetics / Q000473:pathology; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000473:pathology*; D064246:Mad2 Proteins; D008297:Male; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D000075223:Poly-ADP-Ribose Binding Proteins; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
C489444:BUB3 protein, human; D002135:Calcium-Binding Proteins; D018797:Cell Cycle Proteins; C501384:MAD1L1 protein, human; C577697:MAD2L1 protein, human; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D000075223:Poly-ADP-Ribose Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases