S100A7 (Psoriasin), highly expressed in Ductal Carcinoma In Situ(DCIS), is regulated by IFN-gamma in mammary epithelial cells

Abstract

Background: The aim of the present work was to explore signal transduction pathways used in the regulation of S100A7 (psoriasin). Members of the S100 gene family participate in many important cellular functions. Psoriasin, S100A8 (calgranulin A) and S100A9 (calgranulin B) are expressed in ductal carcinoma in situ (DCIS), as well as in the hyperproliferative skin disease, psoriasis. In the latter condition, a disturbance in the STAT pathway has recently been reported. This pathway is implicated in the regulation of IFN-gamma, widely recognized as a key cytokine in psoriasis. IFN-gamma also exerts anti-tumor action in a number of tumor cell types, including breast cancer. We therefore examined the effect of IFN-gamma and STAT-signaling on the psoriasin expression. Methods:We established a TAC2 mouse mammary epithelial cell line with tetracycline-inducible psoriasin expression (Tet-Off). Viability in cell culture was estimated using MTS assay. Protein and gene expression were evaluated by Western blotting and quantitative real-time PCR. Statistical analyses were assessed using a one-tailed, paired t-test. Results:We report the downregulation of psoriasin by IFN-gamma in the MDA-MB-468 breast cancer cell line, as well as the downregulation of psoriasin induced by anoikis in cell lines derived from different epithelial tissues. In contrast, IFN-gamma had no suppressive effect on calgranulin A or calgranulin B. IFN-gamma is an important activator of the STAT1 pathway and we confirmed an active signaling pathway in the cell lines that responded to IFN-gamma treatment. In contrast, in the SUM190 breast carcinoma cell line, IFN-gamma did not suppress the expression of endogenous psoriasin. Moreover, a reduced phosphorylation of the STAT1 protein was observed. We showed that IFN-gamma treatment and the inhibition of the transcription factor NFkappaB had a synergistic effect on psoriasin levels. Finally, in TAC2 cells with tetracycline-induced psoriasin expression, we observed the increased viability of psoriasin-expressing cells after IFN-gamma treatment. Conclusion:Our data support the possibility that psoriasin expression is transcriptionally suppressed by IFN-gamma and that this effect is likely to be mediated by the activation of the STAT1 signaling pathway. The increased viability of psoriasin-expressing cells after IFN-gamma exposure suggests that psoriasin expression leads to the development of an apoptosis-resistant phenotype.

Loss of ICAM-1 signaling induces psoriasin (S100A7) and MUC1 in mammary epithelial cells

“…We have previously shown that IFN-γ down-regulated psoriasin expression induced by suspension culture in normal breast epithelial cells [15]. This finding led to the hypothesis that IFN-γ may interfere with the psoriasin-regulating adhesion signaling that is lost in suspension cultures.…”

“…The MDA-MB-468 (human breast cancer) and the MCF10A (immortalized normal breast epithelium) cell lines were obtained from American Type Culture Collection (Manassas, VA, USA) and were cultivated as previously described [15]. For suspension cultures, cells were plated into poly-2-hydroxy-ethylmethacrylate (polyHEMA) (Sigma Aldrich, Stockholm, Sweden) coated (10mg/cm 2 in 95% ethanol) Petri dishes.…”

“…Western blotting was performed as previously described [15]. Western blotting analyses of cell lysate were produced with anti-psoriasin (mouse-Ab) (Imgenex, San Diego, CA, USA) and anti-calgranulin-B (mouse-Ab) (Dianova GmbH, Hamburg, Germany).…”

Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation

“…Western blotting was performed as previously described [19] and analysis were produced with anti-psoriasin (mouse-Ab) (Imgenex, IMG-409) and anti-GAPDH (rabbit-Ab) (Santa Cruz Biotechnology, sc-25778). Imaging analysis was performed with Alpha Ease FC Software.…”

S100A7 (psoriasin) is induced by the proinflammatory cytokines oncostatin-M and interleukin-6 in human breast cancer

“…It was recently reported that treatment of breast cells with interferon-g, a signature cytokine of cell-mediated (Th1) immune responses, suppressed endogenous S100A7 expression (Petersson et al, 2007). OSM and IL-6 differ from interferon-g in that they function more generally as pleiotropic inflammatory signals.…”