Molecular Profiling of Isolated Histological Components of Wilms Tumor Implicates a Common Role for the Wnt Signaling Pathway in Kidney and Tumor Development
Abstract
Wilms tumor (WT), a tumor composed of three histological components - blastema (BL), epithelia and stroma - is considered an appropriate model system to study the biological relationship between differentiation and tumorigenesis. To investigate molecular associations between nephrogenesis and WT, the gene expression pattern of individual cellular components was analyzed, using a customized platform containing 4,608 genes. WT gene expression patterns were compared to genes regulated during kidney differentiation. BL had a closer gene expression pattern to the earliest stage of normal renal development. The BL gene expression pattern was compared to that of fetal kidney (FK) and also between FK and mature kidney, identifying 25 common deregulated genes supposedly involved in the earliest events of WT onset. Quantitative RT-PCR was performed, confirming the difference in expression levels for 13 of 16 genes (81.2%) in the initial set and 8 of 13 (61.5%) in an independent set of samples. An overrepresentation of genes belonging to the Wnt signaling pathway was identified, namely PLCG2, ROCK2 and adenomatous polyposis coli (APC). Activation of the Wnt pathway was confirmed in WT, using APC at protein level and PLCG2 at mRNA and protein level. APC showed positive nuclear immunostaining for an independent set of WT samples, similarly to the FK in week 11. Lack of PLCG2 expression was confirmed in WT and in FK until week 18. Taken together, these results provided molecular evidence o…
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PLCγ2 was implicated in the Wnt signaling pathway necessary for kidney development and development of Wilms' tumor.
“PLCγ2 was implicated in the Wnt signaling pathway necessary for kidney development and development of Wilms' tumor (144).”
From The role of PLCγ2 in immunological disorders, cancer, and neurodegeneration (2021) · cites this paper as [144]
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- Authors
- Maschietto, M., de Camargo, B., Brentani, H., Grundy, P., Sredni, S. T., Torres, C., Mota, L. D., Cunha, I. W., Patrão, D. F. C., Costa, C. M. L., Soares, F. A., Brentani, R. R., & Carraro, D. M.
- Affiliations
- Universidade de São Paulo (BR)
- University of Alberta (CA)
- Northwestern University (US)
- ORCID
- Venue
- Oncology
- Publisher
- S. Karger AG
- Published
- 2008
- Volume
- 75
- Issue
- 1-2
- Pages
- 81-91
- ISSN
- 0030-2414 (ISSN-L)
- 1423-0232
- OpenAlex
- W2014236942
- Cited by
- 35
- References
- 39
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 1 · 2012: 4
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Oncology (publishedVersion)
- PubMed (publishedVersion)
- Scientific Electronic Library Online (São Paulo Research Foundation, Latin American and Caribbean Center on Health Sciences Information, Conselho Nacional de Desenvolvimento Científico e Tecnológico) (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- UNIFESP Institutional Repository (Universidade Federal de São Paulo) (submittedVersion)
- Funders
- Ludwig Institute for Cancer Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Renal and related cancers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
- Keywords
- Wilms tumor, Wnt signaling, blastema, kidney development, gene expression profiling, PLCγ2, ROCK2, adenomatous polyposis coli, tumor differentiation, embryonic kidney, stroma, tumor onset
- MeSH terms
- Humans, Kidney Neoplasms, Wilms Tumor, Signal Transduction, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Wnt Proteins
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