β-Catenin expression and mutational analysis in renal cell carcinomas

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

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

β-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The β-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β-catenin signaling pathway may partly play a role in the development of conventional RCC.

Original languageEnglish
Pages (from-to)725-730
Number of pages6
JournalPathology International
Volume50
Issue number9
DOIs
Publication statusPublished - 2000 Oct 23

Fingerprint

Catenins
Renal Cell Carcinoma
Mutation
Kidney
Exons
Carcinoma
Wnt Signaling Pathway
Adenomatous Polyposis Coli
Missense Mutation
Tumor Suppressor Genes
Glutamine
DNA Sequence Analysis
Codon
Genes
Arginine
Carcinogenesis
Immunohistochemistry
Cell Proliferation
Apoptosis
Staining and Labeling

Keywords

  • β-catenin
  • Mutation
  • Renal cell carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

β-Catenin expression and mutational analysis in renal cell carcinomas. / Kim, Young Sik; Kang, Yong Koo; Kim, Jung Bun; Han, Seon Ae; Kim, Kwang; Paik, Seung R.

In: Pathology International, Vol. 50, No. 9, 23.10.2000, p. 725-730.

Research output: Contribution to journalArticle

Kim, Young Sik ; Kang, Yong Koo ; Kim, Jung Bun ; Han, Seon Ae ; Kim, Kwang ; Paik, Seung R. / β-Catenin expression and mutational analysis in renal cell carcinomas. In: Pathology International. 2000 ; Vol. 50, No. 9. pp. 725-730.
@article{a1056bdae5554be48df04307b20cd9ae,
title = "β-Catenin expression and mutational analysis in renal cell carcinomas",
abstract = "β-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The β-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β-catenin were observed in five (22.7{\%}) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β-catenin signaling pathway may partly play a role in the development of conventional RCC.",
keywords = "β-catenin, Mutation, Renal cell carcinoma",
author = "Kim, {Young Sik} and Kang, {Yong Koo} and Kim, {Jung Bun} and Han, {Seon Ae} and Kwang Kim and Paik, {Seung R.}",
year = "2000",
month = "10",
day = "23",
doi = "10.1046/j.1440-1827.2000.01111.x",
language = "English",
volume = "50",
pages = "725--730",
journal = "Pathology International",
issn = "1320-5463",
publisher = "Wiley-Blackwell",
number = "9",

}

TY - JOUR

T1 - β-Catenin expression and mutational analysis in renal cell carcinomas

AU - Kim, Young Sik

AU - Kang, Yong Koo

AU - Kim, Jung Bun

AU - Han, Seon Ae

AU - Kim, Kwang

AU - Paik, Seung R.

PY - 2000/10/23

Y1 - 2000/10/23

N2 - β-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The β-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β-catenin signaling pathway may partly play a role in the development of conventional RCC.

AB - β-Catenin acts as a downstream transcriptional activator of the Wingless-Wnt signaling pathway. The β-catenin-Tcf complex transactivates the downstream genes that regulate cell proliferation or inhibit apoptosis. The activation of this pathway through stabilization of β-catenin is caused either by inactivating mutations of adenomatous polyposis coli (APC) tumor suppressor gene or by activating mutations in β-catenin exon 3. To determine whether the abnormal expression and activating mutations in exon 3 of the β-catenin gene are implicated in renal cell carcinogenesis, 52 renal cell carcinomas (RCC) were analyzed by immunohistochemistry, polymerase chain reaction-single-strand conformational polymorphism analysis (PCR-SSCP), and direct DNA sequencing. Immunohistochemically, all cases, as well as normal kidneys, showed membranous and/or cytoplasmic staining patterns without nuclear localization. However, the cytoplasmic accumulations of β-catenin were observed in five (22.7%) of 22 cases of conventional (clear cell) renal carcinoma, but not in papillary or chromophobe renal carcinomas. The β-catenin mutation was identified in only one case of conventional renal carcinoma and was a single-base missense mutation on codon 61, leading to substitution of glutamine by arginine. In conclusion, this study demonstrates that β-catenin mutations are a relatively rare event in RCC and that cytoplasmic accumulations of β-catenin protein are found only in conventional (clear cell) renal carcinomas. These data suggest that the activation of the β-catenin signaling pathway may partly play a role in the development of conventional RCC.

KW - β-catenin

KW - Mutation

KW - Renal cell carcinoma

UR - http://www.scopus.com/inward/record.url?scp=0033780487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033780487&partnerID=8YFLogxK

U2 - 10.1046/j.1440-1827.2000.01111.x

DO - 10.1046/j.1440-1827.2000.01111.x

M3 - Article

C2 - 11012986

AN - SCOPUS:0033780487

VL - 50

SP - 725

EP - 730

JO - Pathology International

JF - Pathology International

SN - 1320-5463

IS - 9

ER -