β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma: Its role in cyclin D1 overexpression and tumor progression

Hideki Shiratsuchi, Torahiko Nakashima, Naoya Hirakawa, Satoshi Toh, Takashi Nakagawa, Tsuyoshi Saito, Masazumi Tsuneyoshi, Shizuo Komune

Research output: Contribution to journalArticle

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Abstract

Background. Nuclear/cytoplasmic accumulation of β-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of β-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of β-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of β-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of β-catenin with the clinical outcome. Methods. Mutations of the β-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of β-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. Results. Nuclear/cytoplasmic accumulation of β-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the β-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed β-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of β-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no β-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with β-catenin accumulation (p = .003). Conclusions. These findings suggest that β-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC.

Original languageEnglish
Pages (from-to)577-584
Number of pages8
JournalHead and Neck
Volume29
Issue number6
DOIs
Publication statusPublished - Jun 1 2007

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Mucoepidermoid Carcinoma
Catenins
Cyclin D1
Neck
Head
Neoplasms
bcl-1 Genes
APC Genes
Wnt Signaling Pathway
Codon
Adenomatous Polyposis Coli Protein
Polymerase Chain Reaction
Neoplasm Staging
Viperidae
Point Mutation

All Science Journal Classification (ASJC) codes

  • Otorhinolaryngology

Cite this

β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma : Its role in cyclin D1 overexpression and tumor progression. / Shiratsuchi, Hideki; Nakashima, Torahiko; Hirakawa, Naoya; Toh, Satoshi; Nakagawa, Takashi; Saito, Tsuyoshi; Tsuneyoshi, Masazumi; Komune, Shizuo.

In: Head and Neck, Vol. 29, No. 6, 01.06.2007, p. 577-584.

Research output: Contribution to journalArticle

Shiratsuchi, H, Nakashima, T, Hirakawa, N, Toh, S, Nakagawa, T, Saito, T, Tsuneyoshi, M & Komune, S 2007, 'β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma: Its role in cyclin D1 overexpression and tumor progression', Head and Neck, vol. 29, no. 6, pp. 577-584. https://doi.org/10.1002/hed.20583
Shiratsuchi, Hideki ; Nakashima, Torahiko ; Hirakawa, Naoya ; Toh, Satoshi ; Nakagawa, Takashi ; Saito, Tsuyoshi ; Tsuneyoshi, Masazumi ; Komune, Shizuo. / β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma : Its role in cyclin D1 overexpression and tumor progression. In: Head and Neck. 2007 ; Vol. 29, No. 6. pp. 577-584.
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title = "β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma: Its role in cyclin D1 overexpression and tumor progression",
abstract = "Background. Nuclear/cytoplasmic accumulation of β-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of β-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of β-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of β-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of β-catenin with the clinical outcome. Methods. Mutations of the β-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of β-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. Results. Nuclear/cytoplasmic accumulation of β-catenin was observed in 6 of 44 MEC cases (13.6{\%}), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the β-catenin gene revealed that 4 of 26 cases (15.4{\%}) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed β-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of β-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no β-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5{\%}). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2{\%}) and was significantly correlated with β-catenin accumulation (p = .003). Conclusions. These findings suggest that β-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC.",
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T1 - β-catenin nuclear accumulation in head and neck mucoepidermoid carcinoma

T2 - Its role in cyclin D1 overexpression and tumor progression

AU - Shiratsuchi, Hideki

AU - Nakashima, Torahiko

AU - Hirakawa, Naoya

AU - Toh, Satoshi

AU - Nakagawa, Takashi

AU - Saito, Tsuyoshi

AU - Tsuneyoshi, Masazumi

AU - Komune, Shizuo

PY - 2007/6/1

Y1 - 2007/6/1

N2 - Background. Nuclear/cytoplasmic accumulation of β-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of β-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of β-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of β-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of β-catenin with the clinical outcome. Methods. Mutations of the β-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of β-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. Results. Nuclear/cytoplasmic accumulation of β-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the β-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed β-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of β-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no β-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with β-catenin accumulation (p = .003). Conclusions. These findings suggest that β-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC.

AB - Background. Nuclear/cytoplasmic accumulation of β-catenin is mainly regulated by its degradation, which is initiated by interaction with adenomatous polyposis coli (APC) protein. Accumulation of β-catenin activates the transcription of 1 of the target oncogenic genes, cyclin D1, in the Wnt/Wingless pathway. The role of β-catenin and cyclin D1 in this pathway has not been previously studied in head and neck mucoepidermoid carcinoma (MEC). This study investigates abnormalities of β-catenin and the APC gene in MEC and correlates the patterns of cyclin D1 overexpression and nuclear/cytoplasmic accumulation of β-catenin with the clinical outcome. Methods. Mutations of the β-catenin and APC genes, as well as overexpression of cyclin D1, were investigated by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in tissue samples from 44 cases of MEC. In addition, we employed differential PCR method to detect amplification of the cyclin D1 gene. Furthermore, the overexpression of cyclin D1 and nuclear/cytoplasmic accumulation of β-catenin was examined by immunohistochemistry, and any correlation with clinicopathologic parameters was evaluated. Results. Nuclear/cytoplasmic accumulation of β-catenin was observed in 6 of 44 MEC cases (13.6%), 5 of which were high-grade MEC, while the other 1 case was intermediate-grade tumor. Mutational analysis of exon 3 of the β-catenin gene revealed that 4 of 26 cases (15.4%) contained point mutations (3 in codon 32, GAC [Asp] to GGC [Gly]; 1 in codon 42, ACA [Thr] to ATA [Ile]), and all these 4 cases showed β-catenin accumulation immunohistochemically. The nuclear/cytoplasmic accumulation of β-catenin was significantly correlated with the adverse outcome of patients (p = .011). Two APC gene alterations were detected in 2 cases of low-grade MEC, where there was no β-catenin nuclear accumulation. Amplification of the cyclin D1 gene was observed in 10 of 26 cases (38.5%). Cyclin D1 overexpression was recognized in 19 of 44 cases (43.2%) and was significantly correlated with β-catenin accumulation (p = .003). Conclusions. These findings suggest that β-catenin, which, in cooperation with cyclin D1, plays crucial role in the Wnt-signaling pathway, may also contribute to the adverse outcome and high-grade tumor staging of MEC.

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