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PMID: 9626060 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

novH: differential expression in developing kidney and Wilm's tumors.

The American journal of pathology ·Vol. 152 ·No. 6 ·1998-06-00 ·Pages 1563-75

Chevalier G, Yeger H, Martinerie C, Laurent M, Alami J, Schofield PN, Perbal B

Abstract

We previously established that the expression of the human nov gene (novH) was altered in Wilms' tumors and that levels of novH and WT1 mRNA were inversely correlated in individual Wilms' tumors. Insofar as novH has been shown to be a target for WT1 regulation, novH might play an important role during normal nephrogenesis and in the development of Wilms' tumors. We now show that during normal nephrogenesis novH protein is tightly associated with differentiation of glomerular podocytes. NovH expression is not restricted to renal differentiation but is also detected in endothelium and neural tissue of the kidney. Our results establish that alteration of novH expression in sporadic and heritable Wilms' tumors is associated with dysregulated expression of both novH mRNA and protein. In general, the highest novH expression was noted in the Wilms' tumor, genitourinary anomalies, aniridia, and mental retardation (WAGR)-associated Wilms' tumors. Expression in the Denys-Drash syndrome (DDS)-associated Wilms' tumors fell within the variable spectrum observed in sporadic Wilms' tumor cases. As in developing kidney podocytes, novH protein was also prominent in the abnormal hypoplastic podocytes from DDS cases and in kidney podocytes adjoining Wilms' tumors. In Wilms' tumors exhibiting heterotypic differentiation, novH protein was expressed at high levels in tumor-derived striated muscle and at lower levels in tumor-derived cartilage. These observations taken together indicate that novH may represent both a marker of podocytic differentiation in kidney and a marker of heterotypic mesenchymal differentiation in Wilms' tumors. In addition, absence or very low levels of WT1 are correlated with higher novH expression, and its variable expression in cases with mutant WT1 (sporadic and DDS) suggests that the potential activation and repression transcriptional functions possessed by WT1 are likely dependent on the specific mutation incurred.

MeSH Terms
Animals Blotting, Western Cells, Cultured Connective Tissue Growth Factor Dogs Gene Expression Regulation Glycosylation Growth Substances/chemistry,metabolism Humans Immediate-Early Proteins/chemistry,metabolism Immunohistochemistry In Situ Hybridization Intercellular Signaling Peptides and Proteins Kidney/growth & development,metabolism Nephroblastoma Overexpressed Protein RNA, Messenger/analysis Time Factors Wilms Tumor/metabolism
Chemicals
CCN2 protein, human CCN3 protein, human Growth Substances Immediate-Early Proteins Intercellular Signaling Peptides and Proteins Nephroblastoma Overexpressed Protein RNA, Messenger Connective Tissue Growth Factor
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Chevalier G
Laboratoire d'Oncologie Virale et Moléculaire, INSERM U142 Hôpital Saint-Antoine, Paris, France.
Yeger H
Martinerie C
Laurent M
Alami J
Schofield P N
Perbal B
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
Published
1998-06-00
Pages
1563-75
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1858457
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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