β‐Catenin expression and mutational analysis in renal cell carcinomas

Kim, Young‐Sik; Kang, Yong Koo; Kim, Jung Bun; Han, Seon Ae; Kim, Kwang Il; Paik, Seung R.

doi:10.1046/j.1440-1827.2000.01111.x

Cited by 46 publications

(40 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Cytoplasmic accumulation of b-catenin was observed in 6 out of 30 tumors in our current study: 1 of 8 Xp11.2 translocation-associated carcinoma, 2 of 4 papillary carcinomas, 1 postneuroblastoma carcinoma, and 2 of 3 renal cell carcinomas associated with nephroblastoma. These findings are in contrast to previous investigations in renal carcinomas in adult patients by Kim et al,18 who reported cytoplasmic b-catenin accumulation in 5 of 22 clear cell carcinomas but none of 10 papillary carcinomas.…”

Section: Discussioncontrasting

confidence: 99%

“…For b-catenin and g-catenin, normal renal tissue was used as internal positive control. Evaluation of immunohistochemical reactivity was performed in a similar way as proposed by Kim et al 18 and as detailed in the Results section below.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…To detect alterations in b-and g-catenin expression in renal cell carcinomas, immunohistochemical reactivity was studied and graded according to signal location and intensity in comparison to epithelia of normal renal tubules in a similar way as proposed by Kim et al 18 Normal renal tissue was present in 20 tumors. In normal renal tissue, b-catenin expression was strong and membranous Wnt signaling in renal cell carcinomas E Bruder et al in epithelia of collecting ducts and Henle loops, whereas proximal and distal tubules showed predominantly cytoplasmic expression of moderate intensity.…”

Section: B-catenin C-catenin and Wt1 Immunohistochemistrymentioning

confidence: 99%

See 2 more Smart Citations

Wnt signaling pathway analysis in renal cell carcinoma in young patients

et al. 2007

View full text Add to dashboard Cite

Renal cell carcinomas in young patients constitute a morphologically and genetically heterogeneous group. Twenty percent belong to the newly recognized Xp11.2 translocation-associated family and rare tumors arise from nephroblastoma. Aberrant Wnt signaling through b-catenin mutation has been implicated in nephroblastoma pathogenesis and has been found to synergize with WT1 mutations. To characterize Wnt signaling activity in renal cell carcinomas in young patients, we gathered 34 tumors (three clear cell, ten Xp11.2 translocation associated, five papillary, two chromophobe, two collecting duct, one neuroblastoma associated, eight unclassified renal cell carcinomas, and three carcinomas combined with nephroblastoma) from patients less than 22 years. Expression of b-catenin, its homologue c-catenin, and of WT1 was assessed by immunohistochemistry in 30 tumors, and sequence analysis of CTNNB1, CTNNG1, and WT1 genes was performed in 25 tumors. Cytoplasmic b-catenin accumulation was demonstrated in two papillary carcinomas, one neuroblastoma-associated carcinoma, and two carcinomas arising from nephroblastoma. The pattern of c-catenin expression paralleled that of b-catenin but its signal intensity was lower in 22, equal in 7, and stronger only in 1 tumor, respectively. Four tumors showed nuclear WT1 expression. One Xp11.2 translocationassociated carcinoma presented a rare intronic CTNNB1 single nucleotide polymorphism and cytoplasmic b-catenin accumulation. There were no further CTNNB1 or CTNNG1 sequence alterations. A WT1 mutation was found in the nephroblastoma component of a carcinoma arising from nephroblastoma. These findings suggest Wnt signaling pathway activation only in a minority of renal cell carcinomas in young patients. CTNNB1 mutations are rare events. Cytoplasmic b-catenin accumulation in an Xp11.2-associated carcinoma suggests potential interaction of Wnt signaling components with microphthalmia transcription factor family also in Xp11.2 translocation carcinomas. WT1 mutation in the nephroblastoma component of a mixed-type renal cell carcinoma provides direct evidence for clonal independence of nephroblastoma and carcinoma components in this exceptional tumor.

show abstract

Section: Discussioncontrasting

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Section: B-catenin C-catenin and Wt1 Immunohistochemistrymentioning

confidence: 99%

See 1 more Smart Citation

Wnt signaling pathway analysis in renal cell carcinoma in young patients

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Initial investigations suggest that activating mutations in ␤-catenin are rare in RCC tumors (39)(40)(41), and no inactivating mutations in APC or axin have been reported in RCC (47,48). Oncogenic ␤-catenin signaling can also be initiated through aberrant Wnt stimulation or loss of negative repressors of Wnt signaling, such as members of the Dkk family.…”

Section: Discussionmentioning

confidence: 99%

The von Hippel–Lindau tumor suppressor gene product represses oncogenic β-catenin signaling in renal carcinoma cells

Peruzzi

Athauda

Bottaro

2006

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Extracted RNAs were reverse-transcribed using oligo (dT) 21 primer and SuperScript II reverse transcriptase (Invitrogen, Carlsbad, CA). Semiquantitative reverse transcription-PCR (RT-PCR) experiments were carried out with the same gene-specific primers as those prepared for constructing our cDNA microarray or with a tubulin-a III (TUBA3)-specific primer as an internal control.…”

Section: Methodsmentioning

confidence: 99%

Hypoxia-Inducible Protein 2 (HIG2), a Novel Diagnostic Marker for Renal Cell Carcinoma and Potential Target for Molecular Therapy

et al. 2005

View full text Add to dashboard Cite

To identify molecules to serve as diagnostic markers for renal cell carcinoma (RCC) and as targets for novel therapeutic drugs, we investigated genome-wide expression profiles of RCCs using a cDNA microarray. We subsequently confirmed that hypoxia-inducible protein-2 (HIG2) was expressed exclusively in RCCs and fetal kidney. Induction of HIG2 cDNA into COS7 cells led to secretion of the gene product into culture medium and resulted in enhancement of cell growth. Small interfering RNA effectively inhibited expression of HIG2 in human RCC cells that endogenously expressed high levels of the protein and significantly suppressed cell growth. Moreover, addition of polyclonal anti-HIG2 antibody into culture medium induced apoptosis in RCC-derived cell lines. By binding to an extracellular domain of frizzled homologue 10 (FZD10), HIG2 protein enhanced oncogenic Wnt signaling and its own transcription, suggesting that this product is likely to function as an autocrine growth factor. ELISA analysis of clinical samples identified secretion of HIG2 protein into the plasma of RCC patients even at an early stage of tumor development, whereas it was detected at significantly lower levels in healthy volunteers or patients with chronic glomerulonephritis. The combined evidence suggests that this molecule represents a promising candidate for development of molecular-targeting therapy and could serve as a prominent diagnostic tumor marker for patients with renal carcinomas. (Cancer Res 2005; 65(11): 4817-26)

show abstract

β‐Catenin expression and mutational analysis in renal cell carcinomas

Cited by 46 publications

References 20 publications

Wnt signaling pathway analysis in renal cell carcinoma in young patients

Wnt signaling pathway analysis in renal cell carcinoma in young patients

The von Hippel–Lindau tumor suppressor gene product represses oncogenic β-catenin signaling in renal carcinoma cells

Hypoxia-Inducible Protein 2 (HIG2), a Novel Diagnostic Marker for Renal Cell Carcinoma and Potential Target for Molecular Therapy

Contact Info

Product

Resources

About