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, <i>Cav-1</i>, resulting in augmented cellular metastasis and invasion, have been demonstrated in various types of cancer, and overexpression of the gene for dynamin-2, <i>DNM2</i>, has been associated with tumorigenesis in cervical, pancreatic and lung cancer. An increased expression of <i>Cav-1</i> and <i>DNM2</i> 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, <i>Cav-1</i> interacts directly with <i>DNM2</i> during the processes. Altered expression of the 2 genes is critical for the normal function of the cell. The expression patterns of <i>Cav-1</i> and <i>DNM2</i> 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 <i>Cav-1</i> and <i>DNM2</i> 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 <i>Cav-1</i> and <i>DNM2</i> (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 <i>Cav-1</i> and <i>DNM2</i> genes, and a determination of their correlation coefficients, may be a potential risk factor for bladder cancer, in addition to other clinical factors.