Bui T D, O'Brien T, Crew J, Cranston D, Harris A L
Imperial Cancer Research Fund, University of Oxford, Institute of Molecular Medicine, John Radcliffe Hospital, UK.
Br J Cancer. 1998;77(2):319-24. doi: 10.1038/bjc.1998.49.
Aberrant Wnt gene expression is involved in the development of breast cancer, but its role in other tumours is unknown. Wnts regulate cadherin function, previously shown to be more commonly deregulated in invasive bladder cancer. This study investigated whether factors upstream of cadherins were aberrantly expressed in superficial bladder cancer. The expression of one transforming (Wnt7b) and one non-transforming (Wnt5a) Wnt gene in four human bladder carcinoma cell lines, and in normal human bladder tissues (n = 8) and bladder cancers (n = 48) were analysed by ribonuclease protection analysis. All cell lines expressed an approximately equal level of Wnt7b mRNA. Wnt5a and Wnt7b mRNAs were both expressed in normal bladder tissues and bladder tumours. The median expression of Wnt7b was fourfold higher in superficial tumours (n = 29) than in normal tissues (n = 8, P = 0.002) and five fold higher than in invasive tumours (n = 17, P = 0.003). There was no significant difference between normal tissues and invasive tumours (P = 0.3). The expression of Wnt5a did not vary significantly between normal tissues and superficial tumours (P = 0.4), normal tissues and invasive tumours (P = 0.3) or superficial tumours and invasive tumours (P = 0.2). The differential expression of Wnt7b suggests a role in the early events of superficial bladder tumorigenesis involving cell adhesion and provides further evidence of different pathways of evolution of superficial and invasive cancer.
异常的Wnt基因表达与乳腺癌的发生发展有关,但其在其他肿瘤中的作用尚不清楚。Wnts调节钙黏蛋白功能,此前研究表明钙黏蛋白功能在浸润性膀胱癌中更常发生失调。本研究调查了钙黏蛋白上游因子在浅表性膀胱癌中是否异常表达。通过核糖核酸酶保护分析,对四种人膀胱癌细胞系、正常人膀胱组织(n = 8)和膀胱癌组织(n = 48)中一种转化型(Wnt7b)和一种非转化型(Wnt5a)Wnt基因的表达进行了分析。所有细胞系中Wnt7b mRNA的表达水平大致相等。Wnt5a和Wnt7b mRNA在正常膀胱组织和膀胱肿瘤中均有表达。Wnt7b在浅表性肿瘤(n = 29)中的中位表达水平比正常组织(n = 8,P = 0.002)高四倍,比浸润性肿瘤(n = 17,P = 0.003)高五倍。正常组织和浸润性肿瘤之间无显著差异(P = 0.3)。Wnt5a在正常组织与浅表性肿瘤之间(P = 0.4)、正常组织与浸润性肿瘤之间(P = 0.3)或浅表性肿瘤与浸润性肿瘤之间(P = 0.2)的表达无显著差异。Wnt7b的差异表达表明其在涉及细胞黏附的浅表性膀胱肿瘤发生早期事件中发挥作用,并为浅表性癌和浸润性癌的不同演变途径提供了进一步证据。