Bilim V, Kawasaki T, Katagiri A, Wakatsuki S, Takahashi K, Tomita Y
Department of Urology, Niigata University School of Medicine, Japan.
Clin Cancer Res. 2000 Feb;6(2):460-6.
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.
正常β-连环蛋白表达缺失及β-连环蛋白基因突变已被证明与多种癌症的恶性特征有关。我们运用聚合酶链反应-单链构象多态性分析及DNA直接测序法，检测了β-连环蛋白第三外显子内的基因改变情况，这些改变在其他肿瘤中较为常见，我们检测了其在移行细胞癌（TCC）和肾细胞癌（RCC）细胞系以及肿瘤标本中的情况。通过免疫组化染色检测了77例原发性和12例转移性RCC以及81例原发性TCC中β-连环蛋白的表达程度及细胞内分布情况。还应用蛋白质印迹分析来确认细胞系和部分肿瘤样本中β-连环蛋白的表达程度。我们未能在RCC和TCC中发现任何基因改变，至少在β-连环蛋白基因的第三外显子中未发现。在部分RCC（15.5%）和TCC（24.7%）中观察到β-连环蛋白的膜免疫反应性降低，这与RCC的晚期阶段和淋巴结受累以及TCC的晚期阶段和多发肿瘤相关。在这项小型研究的能力范围内，β-连环蛋白异常表达与RCC或TCC的复发或生存均无相关性。β-连环蛋白第三外显子的间质缺失和突变在RCC或TCC肿瘤发生中不发挥重要作用。正常β-连环蛋白表达的下调可能有助于RCC和TCC的恶性特征并导致肿瘤进展。然而，这一事件并非复发或肿瘤特异性生存的独立预后因素。
