No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p

<p>Abstract</p> <p>Background</p> <p>The scaffold attachment factor B1 and B2 genes, <it>SAFB1/SAFB2 </it>(both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in <it>SAFB1/SAFB2 </it>have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of <it>SAFB1/SAFB2 </it>on familiar breast cancer by inherited mutations in either of the two genes.</p> <p>Results</p> <p>Mutation analysis in families showing linkage to the <it>SAFB1/2 </it>locus was performed by DNA sequencing. The complete coding sequence of the two genes <it>SAFB1 </it>and <it>SAFB2 </it>was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in <it>SAFB1 </it>and eight polymorphisms were detected in <it>SAFB2</it>. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.</p> <p>Conclusion</p> <p><it>SAFB1 </it>and <it>SAFB2 </it>are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.</p

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

<p>Abstract</p> <p>Background</p> <p>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 <it>in situ </it>(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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

The relation between process creation and the dimensions of intellectual capital : A qualitative study with empirical evidence from the service sector

Studien bidrar till en fördjupad förståelse rörande delkomponenterna inom dimensionerna samt varför hantering av intellektuellt kapital är av vikt inom tjänstesektorn. Genom den presenterade teorisyntesen går det att påvisa att en hantering av intellektuellt kapital i stort bidrar till synergieffekter inom delkomponenterna som i sig bidrar till framgång inom företaget. Vi vill även lyfta fram det teoretiska bidrag som presenterats där vi anser att ett större fokus bör läggas på att lyfta fram vikten hos dimensionen strukturellt kapital och dess delkomponenter för en användning som styrningsverktyg i kontext med resterande dimensioner. The study contributes to a deeper understanding of the subcomponents within the dimensions including why management of intellectual capital is important in the service sector. Through the presented theory synthesis, it is demonstrated that management of intellectual capital contributes largely to synergy effects within the subcomponents, which in itself contributes to success within the company. We also want to highlight the theoretical contribution presented in which we feel that a greater focus should be placed on highlighting the importance of the dimensions within structural capital and its subcomponents for the use as a management tool in context with the remaining dimensions

S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells-1

<p><b>Copyright information:</b></p><p>Taken from "S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells"</p><p>http://www.biomedcentral.com/1471-2407/7/205</p><p>BMC Cancer 2007;7():205-205.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2180183.</p><p></p> reaction (RT-PCR), mRNA level of psoriasin was downregulated in response to IFN-gamma in MCF10A cells () and in MDA-MB-468 cells (). Expression data for psoriasin are presented as ratios, in which the expression data are normalized to an endogenous control (β-actin). Values obtained in control cells were designed as 1 and values obtained from IFN-gamma treated cells were normalized to this from the same run. The data are presented as the mean of three different runs

S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells-3

<p><b>Copyright information:</b></p><p>Taken from "S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells"</p><p>http://www.biomedcentral.com/1471-2407/7/205</p><p>BMC Cancer 2007;7():205-205.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2180183.</p><p></p>MTS-assay on days 3 and 7 and the IFN-gamma/control quotient is demonstrated. Treatment with IFN-gamma produced a 59.5% (day 3) and 32% (day 7) reduction in viability as compared to control cells. The assay was performed in duplicate

S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells-6

<p><b>Copyright information:</b></p><p>Taken from "S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells"</p><p>http://www.biomedcentral.com/1471-2407/7/205</p><p>BMC Cancer 2007;7():205-205.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2180183.</p><p></p>00 u or 1000 u of IFN-gamma. IFN-gamma treatment had no effect on the protein levels of pro-caspase-3. Calgranulin B and calgranulin A () are not influenced by the IFN-gamma treatment. Equal amounts of protein lysate were loaded on the gel. , Treatment with 75 μM HOfor one hour followed by culture for 48 h in regular medium induces the expression of calgranulin A in MCF10A cells. 100 μg of protein lysate were loaded on the gel. , MDA-MB-468 cells with the endogenous expression of psoriasin show the time-dependent repression of psoriasin expression when treated 24, 48 and 72 hours with 1000 u of IFN-gamma. Equal amounts of protein lysate were loaded on the gel. Probing with tubulin/GAPDH assesses the equal loading of the samples. C = cells cultured in monolayer

S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells-4

<p><b>Copyright information:</b></p><p>Taken from "S100A7 (Psoriasin), highly expressed in Ductal Carcinoma (DCIS), is regulated by IFN-gamma in mammary epithelial cells"</p><p>http://www.biomedcentral.com/1471-2407/7/205</p><p>BMC Cancer 2007;7():205-205.</p><p>Published online 6 Nov 2007</p><p>PMCID:PMC2180183.</p><p></p>on with dnIkkβ-virus in MCF10A cells. Neither infection with the different adenoviruses nor the IFN-gamma had any effect on the protein levels of pro-caspase-3. The function of the virus was verified by the accumulation of the IκBα protein. Tubulin assesses equal loading. C control