| 1. |
- Andersson Joona, Pernilla, 1977-, et al.
(författare)
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Temporary agency work and labor migration to Sweden
- 2013
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Ingår i: Labour migrants from Central andEastern Europe in the Nordic countries. - København : Nordisk ministerråd. - 9789289326247 ; , s. 273-299
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 2. |
- Carlström, Maria, et al.
(författare)
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Genetic support for the role of the NLRP3 inflammasome in psoriasis susceptibility
- 2012
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Ingår i: Experimental dermatology. - : John Wiley and Sons. - 0906-6705 .- 1600-0625. ; 21:12, s. 932-937
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Tidskriftsartikel (refereegranskat)abstract
- NACHT leucine-rich repeat- and PYD-containing (NLRP)3 protein controls the inflammasome by regulating caspase-1 activity and interleukin (IL)-1 beta processing. The contribution of IL-1 beta in the pathogenesis of psoriasis is well recognized. Polymorphisms in NLRP3 and caspase recruitment domaincontaining protein (CARD)8, a negative regulator of caspase-1 activity, have been associated with susceptibility to common inflammatory diseases, such as Crohns disease and rheumatoid arthritis. To investigate the role for genetic variants in the NLRP3 inflammasome in psoriasis susceptibility. In a patient sample comprising 1988 individuals from 491 families and 1002 healthy controls, genotypes for four selected single-nucleotide polymorphisms (SNPs) in NLRP3 (three SNPs) and CARD8 (one SNP) were determined by TaqMan (R) Allelic Discrimination. Using the transmission disequilibrium test (TDT), a significant increase in the transmission of the NLRP3 rs10733113G genotype to a subgroup of patients with more widespread psoriasis was demonstrated (P = 0.015). Using logistic regression analysis in 741 patients with psoriasis and 1002 controls, the CARD8 rs2043211 genotype was significantly different in cases and controls in overall terms [OR 1.3 (1.11.5), P = 0.004] and for both genders. Our data support the hypothesis that the inflammasome plays a role in psoriasis susceptibility.
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| 3. |
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| 4. |
- Shubbar, Emman, et al.
(författare)
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Psoriasin (S100A7) increases the expression of ROS and VEGF and acts through RAGE to promote endothelial cell proliferation
- 2012
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 134:1, s. 71-80
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasin (S100A7), originally identified in psoriasis, is a calcium-binding protein belonging to the multigenic S100 family. In high-grade ductal carcinoma in situ, psoriasin was identified as one of the most abundant transcripts. We have previously shown that psoriasin was induced by reactive oxygen species (ROS). Moreover, the downregulation of psoriasin by short hairpin RNA (shRNA) led to the reduced expression of vascular endothelial growth factor (VEGF) and inhibited tumor growth in vivo. The aim of the present study was to investigate whether psoriasin could have direct effects on endothelial cells. In this study we demonstrated that psoriasin increased VEGF expression in mammary epithelial cells. The treatment of endothelial cells with recombinant psoriasin increased proliferation comparable to that of recombinant VEGF protein. No change in proliferation was seen when endothelial cells were infected with psoriasin-expressing adenoviruses, suggesting that the proliferative effect of psoriasin was mediated by a specific receptor. Treatment with sRAGE, targeting the receptor for advanced glycation end products (RAGE), thus inhibited endothelial cell proliferation and tube formation enhanced by recombinant psoriasin. We showed that VEGF expression was not induced by hydrogen peroxide, when psoriasin was silenced by shRNA, which led to the hypothesis that psoriasin induces ROS. Indeed, psoriasin was shown to induce ROS in both endothelial and epithelial cells. Moreover, sRAGE inhibited the psoriasin-dependent generation of ROS in endothelial cells. Finally, treatment with antioxidant Bcl-2 protein abolished the effect of psoriasin on endothelial cell proliferation. Our data suggest that psoriasin expression in mammary epithelial cells leads to increased endothelial cell proliferation in a paracrine manner through RAGE. Psoriasin may therefore play a role in breast cancer progression by promoting oxidative stress response and angiogenesis.
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| 5. |
- Vegfors, Jenny, et al.
(författare)
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The Expression of Psoriasin (S100A7) and CD24 Is Linked and Related to the Differentiation of Mammary Epithelial Cells
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 7:12
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasin (S100A7), a member of the S100 family of calcium-binding proteins, is highly expressed in high-grade ductal carcinoma in situ (DCIS) and in the benign hyperproliferative skin disorder psoriasis. The gene that encodes psoriasin and many other S100 genes are located within a gene cluster on chromosome region 1q21, known as the epidermal differentiation complex. This cluster contains genes for several differentiation markers that play important roles in the terminal differentiation of the epidermis. The purpose of the present study was to evaluate the role of psoriasin in the differentiation process of mammary epithelial cells. Normal mammary epithelial cells (MCF10A) cultured in confluence and suspension, conditions known to induce psoriasin expression, demonstrated a shift towards a more differentiated phenotype indicated by an increase in the expression of the luminal differentiation markers CD24 and MUC1 and the reduced expression of the breast stem cell marker CD44. The expression of psoriasin and MUC1 was most pronounced in the CD24(+)-enriched fraction of confluent MCF10A cells. The shift towards a more differentiated phenotype was abolished upon the downregulation of psoriasin using short hairpin RNA (shRNA) and small interfering RNA (siRNA). Using specific inhibitors, we showed that psoriasin and CD24 expression was regulated by reactive oxygen species (ROS) and the nuclear factor (NF)-kappa B signaling pathways. While immunohistochemical analyses of DCIS showed heterogeneity, the expression of psoriasin and CD24 showed a similar staining pattern. Our findings suggest that the expression of psoriasin is linked to the luminal differentiation marker CD24 in mammary epithelial cells. Psoriasin demonstrated an essential role in the shift towards a more differentiated CD24(+) phenotype, supporting the hypothesis that psoriasin plays a role in the differentiation of luminal mammary epithelial cells.
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| 6. |
- Petersson, Stina, et al.
(författare)
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Loss of ICAM-1 signaling induces psoriasin (S100A7) and MUC1 in mammary epithelial cells
- 2011
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science Business Media. - 0167-6806 .- 1573-7217. ; 125:1, s. 13-25
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Tidskriftsartikel (refereegranskat)abstract
- Psoriasin (S100A7), a member of the S100 gene family, is highly expressed in high-grade comedo ductal carcinoma in situ (DCIS), with a higher risk of local recurrence. Psoriasin is, therefore, a potential biomarker for DCIS with a poor prognosis. High-grade DCIS is characterized by a high proliferation rate and crowded cells, consequently, lose contact with the extracellular matrix. The aim of this study was, therefore, to elucidate the involvement of adhesion signals in the regulation of psoriasin. Protein expression was evaluated by Western blotting, flow cytometry, and immunohistochemistry, and using breast carcinoma SAGE databases available from the CGAP website. Intercellular adhesion molecule 1 (ICAM-1) was down-regulated in MCF10A cells using short hairpin RNA. We found a significant negative correlation between the expression of ICAM-1 and psoriasin, and a positive correlation between psoriasin and MUC1 in normal and DCIS SAGE libraries. In a cluster analysis of 34 adhesion molecules and 20 S100 proteins, we showed that SAGE libraries expressing the S100 proteins-psoriasin, calgranulin-A, and calgranulin-B-clustered together. Interestingly, the expression of all the three proteins correlated strongly to the oncogenic MUC1. We confirmed the negative correlation between ICAM-1 and psoriasin/MUC1, when normal and breast cancer cells were cultured in suspension and on collagen, respectively. The down-regulation of ICAM-1 by short hairpin RNA in MCF10A cells led to the induction of psoriasin, calgranulin-A, calgranulin-B, and MUC1, and we demonstrated that these up-regulations were not ROS dependent. By blocking the phospholipase C (PLC)-IP3 pathway in these cells, we showed that the induction of psoriasin diminished. The results suggest that psoriasin is an intracellular calcium-dependent target of the PLC pathway. Our findings suggest that the down-regulation of ICAM-1 in mammary epithelial cells may contribute both to the high expression of psoriasin seen in some high-grade DCIS tumors and to the induction of MUC1.
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| 7. |
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| 8. |
- Petersson, Stina, 1981
(författare)
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Functional genetic studies of Psoriasin: a potential biomarker for breast cancer with a poor prognosis
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common malignancy in women. There is a high degree of heterogeneity in breast tumours and they can be divided into subtypes that have different expression pattern and clinical outcome. Ductal Carcinoma in situ (DCIS) is regarded as a precursor of invasive ductal breast cancer. Some DCIS lesions will not change in many years, while other will rapidly progress into invasive cancer. It is therefore important to be able to distinguish clinical subgroups of DCIS with a high risk of progression to invasive disease. Aim: Psoriasin is one of the most abundant transcripts in high-grade DCIS with higher risk of local recurrence. Psoriasin has been associated with poor clinical outcome, suggesting its potential involvement in tumour progression. To date, several functions of psoriasin have been proposed, but none of these can fully explain its involvement in breast tumour progression. The aim of this thesis was to elucidate the functional relevance of psoriasin for the initiation and progression of DCIS, and to gain insight into regulatory pathways that control the expression. Results: High-grade DCIS is characterised by a high apoptotic rate and reactive oxidant species (ROS) are known to influence this process. We report the induction of psoriasin by ROS in normal mammary epithelial cells. This induction was repressed by the anti-apoptotic protein Bcl-2 and the antioxidant NAC. Normal mammary epithelial cells with a stable retroviral overexpression of psoriasin were significantly more resistant to ROS-induced cell death. Furthermore, we demonstrate that the NF-κB pathway is potentially involved in the induction of psoriasin expression. (Paper I) IFNγ has been shown to exert anti-tumour action in breast cancer. We report the downregulation of psoriasin by IFNγ in a breast cancer cell line and the downregulation of psoriasin induced by culturing mammary epithelial cells in suspension (loss of contact to extracellular matrix). This effect was shown to be mediated by the activation of the STAT1 signalling pathway. In a mouse mammary epithelial cell line with tetracycline-induced psoriasin expression, we observed the increased viability of psoriasin-expressing cells after IFNγ treatment. (Paper II) The massive induction of psoriasin in suspension culture compared to other stimuli (starvation, confluence and ROS) suggests that changes in adhesion to the extracellular matrix may contribute to the expression of psoriasin. We showed that the downregulation of intercellular adhesion molecule 1 (ICAM-1) (by short hairpin RNA) in mammary epithelial cells increased the expression of psoriasin, through the phospholipase C (PLC)-IP3 pathway, as well as the oncogenic protein mucin1 (MUC1). (Paper III) The interaction between breast epithelial cells and the extracellular matrix contribute to pathological processes and to the normal development of a differentiated structure. Psoriasin has previously been related to epithelial cell differentiation in the skin. We now report that mammary epithelial cells shifted from a CD44+/CD24- to a CD44-/CD24+ phenotype (representing differentiated luminal epithelia) when cultured in confluent and suspension conditions. Interestingly, this result was not observed when psoriasin was suppressed using short hairpin RNA. (Paper IV) Conclusions: We have shown data suggesting that the high expression of psoriasin in high-grade DCIS tumours may be dependent on the production of ROS and a change in adhesion to the ECM, involving ICAM-1 and MUC1. The psoriasin expression leads to increased survival of the breast epithelial cells. Our data also reveal that psoriasin is tightly linked to the expression of CD24. Therefore, it is likely that psoriasin play a role in the differentiation of mammary epithelial cells.
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| 9. |
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| 10. |
- Petersson, Stina, 1981, et al.
(författare)
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S100A7 (Psoriasin), highly expressed in ductal carcinoma in situ (DCIS), is regulated by IFN-gamma in mammary epithelial cells.
- 2007
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Ingår i: BMC Cancer. - : BIOMED CENTRAL LTD. ; 7:205
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Tidskriftsartikel (refereegranskat)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.
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