Expression of the IAP protein family acts cooperatively to predict prognosis in human bladder cancer patients

Abstract

The inhibitors of apoptosis (IAPs) are a group of anti-apoptotic factors in the apoptotic pathway that render cancer cells insensitive to apoptotic stimulation. Recently, several members of the IAP family have been investigated in the context of bladder cancer, and some of these have been associated with specific clinical and pathological tumor features, and with prognosis. These data suggested that the expression of an individual nuclear IAP has an important relationship with the progression of bladder cancer. To date, there are no studies concerning the overall tendencies of IAPs and their comparative therapeutic values in bladder cancer. In this study, we investigated the overall expression trends of the five tumor-related proteins, Survivin, cIAP1, cIAP2, XIAP and Livin, in normal bladder tissues and bladder cancer tissues. We classified and compared the gene expression data of these IAPs with the corresponding clinical and pathological tumor features, and with prognosis, in the development and progression of bladder cancer. The differences in IAP expression levels between archival bladder specimens from 36 normal controls and 105 patients who underwent surgery at our facility were examined using western blot analysis. The localization and expression level of each protein in low- and high-grade bladder cancer tissues were examined through immunohistochemistry. The cytoplasmic expression levels of each protein were scored as 0 (negative), +1 (weak), +2 (medium) or +3 (strong). The nuclear expression levels of cIAP1 and Survivin were scored as 0 (0%), +1 (1–25%), +2 (26–50%) or +3 (>50%). The results demonstrated that the expression of IAPs acted cooperatively to predict prognosis in human bladder cancer patients.

Effects of siRNA Livin on EJ human bladder cancer cells treated with mitomycin-C

“…As a novel member of the inhibitor of apoptosis protein, Livin has been demonstrated to promote cellular proliferation and result in the resistance of tumors to chemotherapeutic medications under overexpression conditions (1). Livin was also revealed to be involved in the apoptosis of human bladder cancer cells through caspase-3 (2) and closely associated with recurrent bladder cancer, indicating the significance of Livin in the treatment of bladder cancer (1,3).…”

“…Livin was also revealed to be involved in the apoptosis of human bladder cancer cells through caspase-3 (2) and closely associated with recurrent bladder cancer, indicating the significance of Livin in the treatment of bladder cancer (1,3). Mitomycin-C (MMC) is a widely used antitumor chemical and is suggested to be useful in treating non-invasive bladder tumors (4), while the suppression of Livin may increase the apoptosis of bladder cancer T24 cells induced by MMC (5).…”

The effects of Livin shRNA on the response to cisplatin in HepG2 cells

“…Livin is a member of the inhibitor of the apoptosis (IAP) family and the baculoviral IAP repeat-containing 7 (BIRC7) gene that encodes Livin is located on human chromosome 20q13.3, is 46 kb in length and comprises 7 exons and 6 introns (2). Overexpression of Livin has been observed in certain types of cancer tissues and cell lines (3).…”

“…This may inhibit the cellular apoptosis induced by several anticancer agents. It is also associated with drug resistance in cancer cells (2,4,5). RNA interference (RNAi) is the phenomenon by which double-stranded RNA molecules homologous to a target gene are processed by the enzyme Dicer to produce active small interfering RNA (siRNA) molecules.…”

“…The RISC, guided by the siRNA, binds to and specifically cleaves mRNA from the target gene, leading to its degradation. This is one form of post-translational gene silencing (2).…”