The murine Pou6f2 gene is temporally and spatially regulated during kidney embryogenesis and its human homolog is overexpressed in a subset of Wilms tumors.
We have previously suggested the transcription factor gene POU6F2 as a novel tumor suppressor involved in Wilms tumor (WT) predisposition. Since WT arises from pluripotent embryonic renal precursors, in this study we analyzed the expression of the murine homolog Pou6f2 during kidney embryogenesis and compared it to that of Wt1, the homolog of WT1, a known WT related gene involved in mesenchyme to epithelium conversion. Quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) performed for Pou6f2 on kidney specimens from embryos, pups, and adult mice, showed that the Pou6f2 mRNA was more abundant in the earliest analyzed phase of kidney organogenesis (E13) than in more advanced fetal stages and in adult animal. In situ RT-PCR demonstrated that Pou6f2 expression parallels the centripetal differentiation of renal morphogenesis. In addition, in E18 kidney, most structures exhibiting Pou6f2 expression stained positively in immunohistochemistry for the Wt1 protein. Finally, quantitative real-time RT-PCR revealed an overexpression (>/=80 times) of POU6F2 compared with normal kidney in 5 of 22 (23%) WTs. The finding of a highly regulated temporal and spatial Pou6f2 expression during renal organogenesis, of its coexpression with Wt1 and of POU6F2 overexpression in a subset of WTs are consistent with a role of POU6F2 in kidney development and provide further support to its involvement in WT.
Di Renzo
Francesca
F
Department of Biology, University of Milan, Milan, Italy.
Doneda
Luisa
L
Menegola
Elena
E
Sardella
Michele
M
De Vecchi
Giovanna
G
Collini
Paola
P
Spreafico
Filippo
F
Fossati-Bellani
Franca
F
Giavini
Erminio
E
Radice
Paolo
P
Perotti
Daniela
D
D000328:Adult; D000368:Aged; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007668:Kidney / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008648:Mesoderm / Q000378:metabolism / Q000473:pathology; D051379:Mice; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology; D038081:Organogenesis / Q000235:genetics; D050809:POU Domain Factors / Q000096:biosynthesis* / Q000235:genetics; D025721:WT1 Proteins / Q000096:biosynthesis* / Q000235:genetics; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D050809:POU Domain Factors; C098906:POU6F2 protein, human; D025721:WT1 Proteins