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Loss of membranous expression of β-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by Exon 3 mutations

(2002) MODERN PATHOLOGY. 15(4). p.454-461
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Abstract
beta-Catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also plays a role in the Wnt signaling pathway by activating T-cell factor- and lymphoid enhancer factor-regulated gene transcription. The level of beta-catenin in cells is tightly controlled in a multiprotein complex, and mutations in the glycogen synthase kinase 3beta (GSK-3beta) phosphorylation sites of the beta-catenin gene (CTNNB1) result in nuclear and/or cytoplasmic accumulation of beta-catenin and constitutive transactivation of T-cell factor and lymphoid enhancer factor target genes, a mechanism occurring in many cancers. Melanoma cell lines may harbor beta-catenin mutations; in vivo, however, cellular accumulation of beta-catenin is rarely caused by CTNNB1 mutations. In our study, 43 primary cutaneous melanoma and 30 metastases were screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel electrophoresis technique and sequencing. beta-Catenin mutations were found in 2 primary melanomas and 1 metastatic melanoma and were not correlated with nuclear accumulation of beta-catenin in these cases. Cellular expression of beta-catenin was evaluated by immunohistochemistry and by reverse polymerase chain reaction (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry revealed a significant loss of membranous P-catenin staining between the primary and metastatic melanomas as well as between radial and vertical growth phase. RT-PCR showed a significant inverse correlation between the amount of RNA and the proportion of cells with membranous expression of beta-catenin (P = .0015); no correlation existed between the amount of RNA and the number of cells with nuclear or cytoplasmic expression of G-catenin. In conclusion, nuclear expression of beta-catenin is seen in cutaneous melanoma but, in contrast to the case of many other cancers, does not correlate with tumor stage or mutation status. A combination of immunohistochemistry and RTPCR showed that down-regulation of membranous beta-catenin was associated with an increased amount of beta-catenin RNA in primary or metastatic melanoma. Our results suggest that posttranslational events, rather than CTNNB1 mutations, are responsible for the altered distribution of beta-catenin in cutaneous melanoma.
Keywords
DGGE, beta-catenin, immmohistochemistry, melanoma, RT-PCR, tumorigenesis, E-CADHERIN, HEPATOCELLULAR CARCINOMAS, FUNCTIONAL INTERACTION, MALIGNANT-MELANOMA, PROSTATE-CANCER, ALPHA-CATENIN, CELL-LINES, GENE, APC, ACTIVATION

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Chicago
Demunter, Anouk, Louis Libbrecht, Hugo Degreef, Chris De Wolf-Peeters, and Joost J van den Oord. 2002. “Loss of Membranous Expression of Β-catenin Is Associated with Tumor Progression in Cutaneous Melanoma and Rarely Caused by Exon 3 Mutations.” Modern Pathology 15 (4): 454–461.
APA
Demunter, A., Libbrecht, L., Degreef, H., De Wolf-Peeters, C., & van den Oord, J. J. (2002). Loss of membranous expression of β-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by Exon 3 mutations. MODERN PATHOLOGY, 15(4), 454–461.
Vancouver
1.
Demunter A, Libbrecht L, Degreef H, De Wolf-Peeters C, van den Oord JJ. Loss of membranous expression of β-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by Exon 3 mutations. MODERN PATHOLOGY. 2002;15(4):454–61.
MLA
Demunter, Anouk, Louis Libbrecht, Hugo Degreef, et al. “Loss of Membranous Expression of Β-catenin Is Associated with Tumor Progression in Cutaneous Melanoma and Rarely Caused by Exon 3 Mutations.” MODERN PATHOLOGY 15.4 (2002): 454–461. Print.
@article{3183208,
  abstract     = {beta-Catenin plays a fundamental role in the regulation of the E-cadherin-catenin cell adhesion complex. It also plays a role in the Wnt signaling pathway by activating T-cell factor- and lymphoid enhancer factor-regulated gene transcription. The level of beta-catenin in cells is tightly controlled in a multiprotein complex, and mutations in the glycogen synthase kinase 3beta (GSK-3beta) phosphorylation sites of the beta-catenin gene (CTNNB1) result in nuclear and/or cytoplasmic accumulation of beta-catenin and constitutive transactivation of T-cell factor and lymphoid enhancer factor target genes, a mechanism occurring in many cancers. Melanoma cell lines may harbor beta-catenin mutations; in vivo, however, cellular accumulation of beta-catenin is rarely caused by CTNNB1 mutations. In our study, 43 primary cutaneous melanoma and 30 metastases were screened for CTNNB1 exon 3 mutations by using a denaturing gradient gel electrophoresis technique and sequencing. beta-Catenin mutations were found in 2 primary melanomas and 1 metastatic melanoma and were not correlated with nuclear accumulation of beta-catenin in these cases. Cellular expression of beta-catenin was evaluated by immunohistochemistry and by reverse polymerase chain reaction (RT-PCR) in 80 and 70 cases, respectively. Immunohistochemistry revealed a significant loss of membranous P-catenin staining between the primary and metastatic melanomas as well as between radial and vertical growth phase. RT-PCR showed a significant inverse correlation between the amount of RNA and the proportion of cells with membranous expression of beta-catenin (P = .0015); no correlation existed between the amount of RNA and the number of cells with nuclear or cytoplasmic expression of G-catenin. In conclusion, nuclear expression of beta-catenin is seen in cutaneous melanoma but, in contrast to the case of many other cancers, does not correlate with tumor stage or mutation status. A combination of immunohistochemistry and RTPCR showed that down-regulation of membranous beta-catenin was associated with an increased amount of beta-catenin RNA in primary or metastatic melanoma. Our results suggest that posttranslational events, rather than CTNNB1 mutations, are responsible for the altered distribution of beta-catenin in cutaneous melanoma.},
  author       = {Demunter, Anouk and Libbrecht, Louis and Degreef, Hugo and De Wolf-Peeters, Chris and van den Oord, Joost J},
  issn         = {0893-3952},
  journal      = {MODERN PATHOLOGY},
  keywords     = {DGGE,beta-catenin,immmohistochemistry,melanoma,RT-PCR,tumorigenesis,E-CADHERIN,HEPATOCELLULAR CARCINOMAS,FUNCTIONAL INTERACTION,MALIGNANT-MELANOMA,PROSTATE-CANCER,ALPHA-CATENIN,CELL-LINES,GENE,APC,ACTIVATION},
  language     = {eng},
  number       = {4},
  pages        = {454--461},
  title        = {Loss of membranous expression of β-catenin is associated with tumor progression in cutaneous melanoma and rarely caused by Exon 3 mutations},
  url          = {http://dx.doi.org/10.1038/modpathol.3880546},
  volume       = {15},
  year         = {2002},
}

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