Caveolin-1 and dynamin-2 overexpression is associated with the progression of bladder cancer

Abstract

Caveolae-mediated endocytosis regulates cell adhesion and growth in an anchorage-dependent manner. Studies of the endocytic function of caveolae have suggested a wide-ranging list of cargoes, including a number of receptors and extracellular proteins, ligands and nutrients from the extracellular matrix. Disruption of the processes of caveolae-mediated endocytosis mediated by signaling proteins is critical to cellular integrity. Caveolin-1 and dynamin-2 are the 2 major proteins associated with endocytotic function. Mechanistically, dynamin-2 has a co-equal role with caveolin-1 in terms of caveolae-derived endosome formation. Recent studies have revealed the pathological outcomes associated with the dysregulation of caveolin-1 and dynamin-2 expression. Increased expression levels of the gene for caveolin, Cav-1, resulting in augmented cellular metastasis and invasion, have been demonstrated in various types of cancer, and overexpression of the gene for dynamin-2, DNM2, has been associated with tumorigenesis in cervical, pancreatic and lung cancer. An increased expression of Cav-1 and DNM2 is known to be associated with the invasive behavior of cancer cells, and with cancer progression. Furthermore, it has been previously demonstrated that, in caveolar assembly and caveolae mediated endocytosis, Cav-1 interacts directly with DNM2 during the processes. Altered expression of the 2 genes is critical for the normal function of the cell. The expression patterns of Cav-1 and DNM2 have been previously examined in bladder cancer cell lines, and were each demonstrated to be overexpressed. In the present study, the expression levels of these 2 genes in bladder cancer samples were quantified. The gene expression levels of Cav-1 and DNM2 were identified to be increased 8.88- and 8.62-fold, respectively, in tumors compared with the normal controls. Furthermore, high-grade tumors exhibited significantly increased expression levels of Cav-1 and DNM2 (both P<0.0001) compared with the low-grade tumors. In addition, compared with normal control samples, the expression of the 2 genes in tumor samples was observed to be highly significant (P<0.0001), with a marked positive correlation identified for the tumors (Pearson's correlation coefficient, r=0.80 for the tumor samples vs. r=0.32 in the normal control samples). Taken together, the results of the present study demonstrated that the overexpression of Cav-1 and DNM2 genes, and a determination of their correlation coefficients, may be a potential risk factor for bladder cancer, in addition to other clinical factors.

Keywords: bladder cancer; caveolin-1; dynamin-2.

Figure 1.

Comparison of Cav-1 and DNM2 expression in tumor and adjacent normal bladder tissues using the Wilcoxon test. ****P<0.0001. Cav-1, caveolin-1; DNM2, dynamin-2.

Figure 2.

Comparison of Cav-1 and DNM2 expression in low- and high-grade tumor tissues using the Wilcoxon test. ****P<0.0001. Cav-1, caveolin-1; DNM2, dynamin-2.

Figure 3.

Stage-wise comparison in the expression of (A) Cav-1 and (B) DNM2 in tumor samples. Overall statistical significance was determined using one way analysis of variance followed by Tukey's post-hoc test. ****P<0.0001. Cav-1, caveolin-1; DNM2, dynamin-2.

Figure 4.

Correlation analysis of the expression levels of Cav-1 and DNM2 in (A) the adjacent normal bladder tissue (r=0.32; P=0.05) and (B) the tumor samples (r=0.80; P<0.0001). Cav-1, caveolin-1; DNM2, dynamin-2.