Transmembrane 7 superfamily member 4 regulates cell cycle progression in breast cancer cells.

OBJECTIVE: TM7SF4 (transmembrane 7 superfamily member 4) gene encodes a seven-pass transmembrane protein that is primarily expressed in dendritic cells called as dendritic cell-specific expressed seven transmembrane protein (DC-STAMP). This protein regulates immunological functions, osteoclastogenesis and myeloid differentiation. Although the roles of TM7SF4 have been currently studied on Paget's disease of bone and papillary thyroid cancers, it is unclear whether TM7SF4 plays a role in breast cancer. In current study, we investigated the expression of TM7SF4 in human breast cancer cell lines. MATERIALS AND METHODS: In this study, five breast cancer lines were cultured. Small hairpin RNA against TM7SF4 using a lentiviral vector was generated and transfected into MCF-7 breast cancer cells. Effects of down-regulating TM7SF4 in transfected cells were examined by Western blot, RT-PCR, apoptotic rate, colony formation, and cell cycle analyses. RESULTS: The results demonstrated that down-regulation of TM7SF4 led to a decrease in colony formation in MCF-7 cells compared to the control group. This is likely due to a decrease in proliferation and cell cycle and an increase in apoptosis. CONCLUSIONS: To our knowledge, our data demonstrate for the first time that TM7SF4 plays an essential role in regulating cell cycle progression in breast cancer.

Expression of erythropoietin and its receptor in kidneys from normal and cyclosporine-treated rats.

Long-term treatment with cyclosporine A (CsA) is associated with various types of complications; however, CsA-induced anemia has not been reported. The present study examined the impact of CsA on hematopoietic parameters and intrarenal expression of erythropoietin (EPO) and the EPO receptor (EPOR) in a rat model of chronic CsA nephrotoxicity. Sprague-Dawley rats were fed a low-salt diet (0.05% sodium) and were treated daily for 4 weeks with vehicle (olive oil 1 mL/kg subcutaneously) or CsA (15 mg/kg subcutaneously). The expression of EPO and EPOR was evaluated by immunohistochemistry and immunoblotting, and hematopoietic parameters were assessed by measuring blood hemoglobin and hematocrit levels, and these variables were compared between treatment groups. Renal function, oxidative stress, histopathology (tubulointerstitial fibrosis), apoptotic cell death, and expression of transforming growth factor ß-inducible gene-h3 (ßig-h3) were also compared between treatment groups. In kidneys from vehicle-treated rats, endogenous EPO and EPOR protein were expressed constitutively in the outer stripe of the outer medulla and the cortex. EPO protein expression decreased significantly in kidneys from CsA-treated rats. By contrast, EPOR expression was higher in kidneys from CsA-treated rats than in vehicle-treated rats. These changes were accompanied by decreases in serum hemoglobin and hematocrit levels and correlated with the number of cells positive for terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (r = -0.769, P = .003) and ßig-h3 protein expression (r = -0.910, P < .001). Long-term treatment with CsA suppresses renal endogenous EPO expression, resulting in anemia. Increases in apoptotic cell death and ßig-h3 expression are closely associated with inhibition of EPO expression in chronic CsA nephrotoxicity.

L-carnitine protects against cyclosporine-induced pancreatic and renal injury in rats.

BACKGROUND: L-carnitine has protective effects against various types of injury. This study was designed to evaluate the beneficial effects of L-carnitine on pancreatic and renal injuries caused by cyclosporine (CsA). METHODS: Rats maintained on a low sodium diet were given vehicle (olive oil, 1 mL/kg/d), CsA (15 mg/kg/d), L-carnitine (50 or 200 mg/kg/d), or a combination of CsA and L-carnitine for 4 weeks. The impact of L-carnitine on pancreatic injury was assessed by blood glucose levels, plasma insulin concentrations, and hemoglobulin A1c (HbA1c). In addition, the protective effects of L-carnitine against CsA-induced kidney injury were evaluated in terms of renal function, histopathology (inflammatory cell influx and tubulointerstitial fibrosis), oxidative stress (8-hydroxy 2'-deoxyguanosine, 8-OHdG), transforming growth factor-betal (TGF-ß1), apoptosis (caspase-3), and autophagy (LC3-II). RESULTS: CsA treatment caused diabetes, renal dysfunction, tubulointerstitial inflammation (ED-1-positive cells), and fibrosis, which were accompanied by an increase in 8-OHdG production and upregulation of TGF-ß1, caspase-3, and LC3-II. Concomitant administration of L-carnitine increased plasma insulin concentrations, decreasing plasma glucose and HbA1c levels. In the kidney, L-carnitine induced dose-dependent improvement of renal function, inflammation, and fibrosis in parallel with suppression of the expression of TGF-ß1 and 8-OHdG. Furthermore, the administration of L-carnitine at a high dose inhibited the expression of caspase-3 and LC3-II. CONCLUSION: These findings suggest that L-carnitine has a protective effect against CsA-induced pancreatic and renal injuries.