Altered expression of beta-catenin in renal cell cancer and transitional cell cancer with the absence of beta-catenin gene mutations.

Abstract

Loss of normal beta-catenin expression and the beta-catenin gene mutations have been shown to contribute to the malignant character of various cancers. Using PCR-single-strand conformation polymorphism and DNA direct sequencing, we examined the presence of genetic alterations within the third exon of beta-catenin, which are frequently observed in other tumors, in transitional cell cancer (TCC) and renal cell cancer (RCC) cell lines, and in tumor specimens. The degrees of expression and intracellular distribution of beta-catenin were detected by immunohistochemical staining in 77 primary and 12 metastatic RCCs and in 81 primary TCCs. Western blot analysis was also applied to confirm the degree of beta-catenin expression in the cell lines and some tumor samples. We failed to reveal any genetic alterations, at least in the third exon of the beta-catenin gene, in RCC and TCC. Reduced membranous immunoreactivity of beta-catenin was observed in portions of RCC (15.5%) and TCC (24.7%) and was correlated with advanced stages and nodal involvement in RCC and with advanced stages and multiple tumors in TCC. Within the power limitations of this small study, beta-catenin abnormal expression was not correlated with recurrence or survival in either RCC or TCC. Interstitial deletions and mutations in the third exon of beta-catenin do not play a significant role in RCC or TCC tumorigenesis. Down-regulation of normal beta-catenin expression might contribute to the malignant character of RCC and TCC and result in tumor progression. However, this event is not an independent prognostic factor for recurrence or tumor specific survival.

• Authors: V Bilim, T Kawasaki, A Katagiri, S Wakatsuki, K Takahashi, Y Tomita
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 6 Issue 2 Pg. 460-6 (Feb 2000) ISSN: 1078-0432 [Print] United States
• PMID: 10690524 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• CTNNB1 protein, human
• Cadherins
• Cytoskeletal Proteins
• Trans-Activators
• beta Catenin

Topics

• Adult
• Aged
• Aged, 80 and over
• Amino Acid Sequence
• Base Sequence
• Cadherins (genetics)
• Carcinoma, Renal Cell (genetics, mortality, pathology, surgery)
• Carcinoma, Transitional Cell (genetics, mortality, pathology, surgery)
• Cytoskeletal Proteins (analysis, genetics)
• Exons
• Female
• Follow-Up Studies
• Gene Expression Regulation, Neoplastic
• Humans
• Kidney Neoplasms (genetics, mortality, pathology, surgery)
• Male
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Survival Analysis
• Time Factors
• Trans-Activators
• Tumor Cells, Cultured
• Urologic Neoplasms (genetics, mortality, pathology, surgery)
• beta Catenin