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Article ; Online: Expression of Concern: Leukotriene D4 activates MAPK through a Ras-independent but PKCε-dependent pathway in intestinal epithelial cells.

Paruchuri, Sailaja / Hallberg, Bengt / Juhas, Maria / Larsson, Christer / Sjölander, Anita

2023 Volume 136, Issue 8

Language	English
Publishing date	2023-04-26
Publishing country	England
Document type	Journal Article ; Expression of Concern
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.261243
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Article ; Online: The combination of TRAIL and the Smac mimetic LCL-161 induces an irreversible phenotypic change of MCF-7 breast cancer cells.

Granqvist, Victoria / Holmgren, Christian / Larsson, Christer

Experimental and molecular pathology

2022 Volume 125, Page(s) 104739

Abstract: Introduction: Breast cancer is the most common malignancy affecting women. Although the prognosis generally is good, a substantial number of patients still suffer from relapse, emphasizing the need for novel treatments. Smac mimetics were developed to ... ...

Abstract	Introduction: Breast cancer is the most common malignancy affecting women. Although the prognosis generally is good, a substantial number of patients still suffer from relapse, emphasizing the need for novel treatments. Smac mimetics were developed to facilitate cell death by blocking inhibitor of apoptosis proteins (IAPs). It has been suggested that TNF-related apoptosis inducing ligand (TRAIL) can be used together with Smac mimetics to induce cancer cell death. Methods: Cell viability was studied with Trypan blue staining and Annexin V assay, siRNA was used to downregulate specific proteins, protein levels were estimated with Western blot, and mRNA levels were analyzed with qPCR, microarray and RNA-seq. For global expression, groups were compared with principal component analysis and the limma package in R. Gene enrichment was analyzed with Fisher's test. For other experiments, significance of difference was tested by one-way ANOVA, followed by Tukey's HSD test. Results: The combination of Smac mimetic LCL-161 and TRAIL induces an irreversible change in phenotype, but not cell death, of luminal MCF-7 breast cancer cells. The cells become small and circular and dissociate from each other and the effect could not be reversed by returning the cells to regular growth medium. The morphology change could be prevented by caspase inhibition using z-VAD-FMK and downregulation of caspase-8. Caspase-7 is also indicated to be of importance since downregulation of this caspase resulted in fewer morphologically changed cells. Enrichment analyses of changes in global gene expression demonstrated that genes associated with estrogen receptor (ER) signaling are downregulated, whereas nuclear factor kappa B- (NF-κB) and interferon- (IFN) driven genes are upregulated in altered cells. However, inhibition of these pathways did not influence the change in morphology. Induction of IFN-induced genes were potentiated but NF-ĸB-driven genes were slightly suppressed by caspase inhibition. Conclusions: The results demonstrate that LCL-161 and TRAIL can irreversibly alter the MCF-7 breast cancer cell phenotype. However, the changes in morphology and global gene expression are mediated via separate pathways.
MeSH term(s)	Apoptosis ; Breast Neoplasms/drug therapy ; Breast Neoplasms/genetics ; Breast Neoplasms/metabolism ; Caspases/metabolism ; Caspases/pharmacology ; Cell Line, Tumor ; Female ; Humans ; Inhibitor of Apoptosis Proteins ; MCF-7 Cells ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Neoplasm Recurrence, Local ; Phenotype ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; TNF-Related Apoptosis-Inducing Ligand/pharmacology
Chemical Substances	Inhibitor of Apoptosis Proteins ; NF-kappa B ; TNF-Related Apoptosis-Inducing Ligand ; Caspases (EC 3.4.22.-)
Language	English
Publishing date	2022-01-07
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	207655-x
ISSN	1096-0945 ; 0014-4800
ISSN (online)	1096-0945
ISSN	0014-4800
DOI	10.1016/j.yexmp.2021.104739
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Book ; Thesis: Ethanol and muscarinic receptor stimulated signal transduction in nerve cells

Larsson, Christer

1995

Author's details	by Christer Larsson
Language	English
Size	Getr. Zählung : Ill., graph. Darst.
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Lund, Univ., Diss., 1995
Note	Zsfassung in schwed. Sprache
HBZ-ID	HT006751144
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Article ; Online: "Association of mammographic features with molecular breast tumor profiles".

Sartor, Hanna / Zackrisson, Sophia / Hegardt, Cecilia / Larsson, Christer

Cancer treatment and research communications

2021 Volume 28, Page(s) 100387

Abstract: Purpose: Mammographic density and tumor appearance are breast cancer prognostic factors. Conceivably, mammographic features are macroscopic reflections of tumor´s molecular composition, but to an unknown extent. Our aim was to study associations of ... ...

Abstract	Purpose: Mammographic density and tumor appearance are breast cancer prognostic factors. Conceivably, mammographic features are macroscopic reflections of tumor´s molecular composition, but to an unknown extent. Our aim was to study associations of mammographic features with molecular tumor profiles. Methods: Invasive breast cancers (2007-2016) in Malmö Diet and Cancer Study (MDCS) for which there were tumor RNA-sequencing analyses within Sweden Cancerome Analysis Network - Breast (SCAN-B) (n=102) or All Breast Cancer in Malmö (ABIM) (n=50) were identified. Density (fatty vs. dense), tumor appearance (mass vs. spiculation), and intrinsic subtypes were registered. Differences in gene/metagene expression and Microenvironment Cell Population Counter were analyzed with R. Overall survival was used as endpoint. Results: No gene expression differences between density groups was observed. In one cohort (but not the other), Luminal A tumors associated with fatty breasts. For spiculation vs. mass, (p<0.01, t-test) 86 genes were differentially expressed; only one gene was differentially expressed comparing density. Gene set enrichment analysis showed genes highly expressed in spiculated tumors were enriched for extracellular matrix-associated genes whereas genes highly expressed with masses were associated with proliferation. A spiculation metagene, based on differentially expressed genes, showed association with estrogen receptor positivity, lower grade, and improved survival, but it was not an independent prognostic factor. Conclusion: There are clear differences in molecular composition between breast tumors with a spiculated appearance vs. a mass as the dominant tumor appearance. However, there are no apparent molecular differences related to the density of the breast in which the tumor has arisen.
MeSH term(s)	Aged ; Aged, 80 and over ; Breast/diagnostic imaging ; Breast/pathology ; Breast Density ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mammography ; Metagenome ; Middle Aged ; Sweden
Language	English
Publishing date	2021-05-09
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2468-2942
ISSN (online)	2468-2942
DOI	10.1016/j.ctarc.2021.100387
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Article ; Online: Induction of interferon-β and interferon signaling by TRAIL and Smac mimetics via caspase-8 in breast cancer cells.

Granqvist, Victoria / Holmgren, Christian / Larsson, Christer

PloS one

2021 Volume 16, Issue 3, Page(s) e0248175

Abstract: Breast cancer prognosis is frequently good but a substantial number of patients suffer from relapse. The death receptor ligand TRAIL can in combination with Smac mimetics induce apoptosis in some luminal-like ER-positive breast cancer cell lines, such as ...

Abstract	Breast cancer prognosis is frequently good but a substantial number of patients suffer from relapse. The death receptor ligand TRAIL can in combination with Smac mimetics induce apoptosis in some luminal-like ER-positive breast cancer cell lines, such as CAMA-1, but not in MCF-7 cells. Here we show that TRAIL and the Smac mimetic LCL161 induce non-canonical NF-κB and IFN signaling in ER-positive MCF-7 cells and in CAMA-1 breast cancer cells when apoptosis is blocked by caspase inhibition. Levels of p52 are increased and STAT1 gets phosphorylated. STAT1 phosphorylation is induced by TRAIL alone in MCF-7 cells and is independent of non-canonical NF-κB since downregulation of NIK has no effect. The phosphorylation of STAT1 is a rather late event, appearing after 24 hours of TRAIL stimulation. It is preceded by an increase in IFNB1 mRNA levels and can be blocked by siRNA targeting the type I IFN receptor IFNAR1 and by inhibition of Janus kinases by Ruxolitinib. Moreover, downregulation of caspase-8, but not inhibition of caspase activity, blocks TRAIL-mediated STAT1 phosphorylation and induction of IFN-related genes. The data suggest that TRAIL-induced IFNB1 expression in MCF-7 cells is dependent on a non-apoptotic role of caspase-8 and leads to autocrine interferon-β signaling.
MeSH term(s)	Antineoplastic Agents/metabolism ; Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/metabolism ; Apoptosis Regulatory Proteins/pharmacology ; Breast Neoplasms/drug therapy ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Caspase 8/metabolism ; Cell Line, Tumor ; Female ; Humans ; Interferon-beta/metabolism ; MCF-7 Cells ; Mitochondrial Proteins/metabolism ; Mitochondrial Proteins/pharmacology ; Signal Transduction/drug effects ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; TNF-Related Apoptosis-Inducing Ligand/pharmacology ; Thiazoles/metabolism ; Thiazoles/pharmacology
Chemical Substances	Antineoplastic Agents ; Apoptosis Regulatory Proteins ; DIABLO protein, human ; LCL161 ; Mitochondrial Proteins ; TNF-Related Apoptosis-Inducing Ligand ; TNFSF10 protein, human ; Thiazoles ; Interferon-beta (77238-31-4) ; CASP8 protein, human (EC 3.4.22.-) ; Caspase 8 (EC 3.4.22.-)
Language	English
Publishing date	2021-03-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0248175
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Article ; Online: Induction of Breast Cancer Cell Apoptosis by TRAIL and Smac Mimetics: Involvement of RIP1 and cFLIP.

Holmgren, Christian / Sunström Thörnberg, Ellen / Granqvist, Victoria / Larsson, Christer

Current issues in molecular biology

2022 Volume 44, Issue 10, Page(s) 4803–4821

Abstract: Smac mimetics are a group of compounds able to facilitate cell death in cancer cells. TNF-related apoptosis-inducing ligand (TRAIL) is a death receptor ligand currently explored in combination with Smac mimetics. The molecular mechanisms determining if ... ...

Abstract	Smac mimetics are a group of compounds able to facilitate cell death in cancer cells. TNF-related apoptosis-inducing ligand (TRAIL) is a death receptor ligand currently explored in combination with Smac mimetics. The molecular mechanisms determining if the combination treatment results in apoptosis are however not fully understood. In this study, we aimed to shed light on these mechanisms in breast cancer cells. Three breast cancer cell lines, MDA-MB-468, CAMA-1 and MCF-7, were used to evaluate the effects of Smac mimetic LCL-161 and TRAIL using cell death assays and Western blot. The combination treatment induces apoptosis and caspase-8 cleavage in MDA-MB-468 and CAMA-1 but not in MCF-7 cells and downregulation of caspase-8 blocked apoptosis. Downregulation, but not kinase inhibition, of receptor-interacting protein 1 (RIP1) suppressed apoptosis in CAMA-1. Apoptosis is preceded by association of RIP1 with caspase-8. Downregulating cellular FLICE-like inhibitory protein (c-FLIP) resulted in increased caspase cleavage and some induction of apoptosis by TRAIL and LCL-161 in MCF-7. In CAMA-1, c-FLIP depletion potentiated TRAIL-induced caspase cleavage and LCL-161 did not increase it further. Our results lend further support to a model where LCL-161 enables the formation of a complex including RIP1 and caspase-8 and circumvents c-FLIP-mediated inhibition of caspase activation.
Language	English
Publishing date	2022-10-11
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2000024-8
ISSN	1467-3045 ; 1467-3037
ISSN (online)	1467-3045
ISSN	1467-3037
DOI	10.3390/cimb44100327
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Zs.A 5122: Show issues

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Book ; Thesis: Nicotinic receptors in the central nervous system

Larsson, Christer

methodolog. and functional aspects

(Acta Universitatis Upsaliensis : Abstracts of Uppsala dissertations from the Faculty of Pharmacy ; 104)

1985

Series title	Acta Universitatis Upsaliensis : Abstracts of Uppsala dissertations from the Faculty of Pharmacy ; 104 Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis ; Abstracts of Uppsala dissertations from the Faculty of Pharmacy
Collection	Acta Universitatis Upsaliensis Acta Universitatis Upsaliensis ; Abstracts of Uppsala dissertations from the Faculty of Pharmacy
Keywords	Zentralnervensystem ; Nicotin ; Rezeptor ; Gehirn
Subject	Cerebrum ; Hirn ; Encephalon ; Enzephalon ; Hirngewebe ; Hirnmasse ; Gehirnmasse ; Nikotin ; CAS 54-11-5 ; Zentrales Nervensystem ; ZNS ; Systema nervosum centrale ; Central nervous system ; CNS
Size	45 S. : Ill., graph. Darst.
Publisher	Almqvist & Wiksell
Publishing place	Uppsala u.a.
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Uppsala, Univ., Diss., 1985
HBZ-ID	HT002422746
ISBN	91-554-1662-4 ; 978-91-554-1662-1
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Article: Food waste to new food: Risk assessment and microbial community analysis of anaerobic digestate as a nutrient source in hydroponic production of vegetables

Södergren, Julia / Larsson, Christer U. / Wadsö, Lars / Bergstrand, Karl-Johan / Asp, Håkan / Hultberg, Malin / Schelin, Jenny

Journal of cleaner production. 2022 Jan. 20, v. 333

2022

Abstract: In this study, the microbiological food safety of using anaerobic digestate as a fertilizer in hydroponic production of vegetables was evaluated. The used anaerobic digestate was a liquid residue obtained from the digestion of food waste in the ... ...

Abstract	In this study, the microbiological food safety of using anaerobic digestate as a fertilizer in hydroponic production of vegetables was evaluated. The used anaerobic digestate was a liquid residue obtained from the digestion of food waste in the production of biogas. Replacing the customary inorganic fertilizer used in hydroponic production with this recycled fertilizer (biofertilizer) could allow for sustainable urban food production close to retailers and consumers. However, in striving for circular food production, it is vital that the food safety of utilizing recycled resources is ensured. Especially in the application of hydroponic farming, where the nutrient loop is shorter than on arable land, a microbiological food safety risk assessment is crucial when adopting new and recycled fertilizers. The biofertilizer based on anaerobic digestate was therefore studied with regard to its microbial community (16S rRNA gene amplicon sequencing) during production of vegetables in a hydroponic system. The biofertilizer was also challenge tested with food borne pathogens (Salmonella enterica, Listeria monocytogenes and Bacillus cereus). Furthermore, the microbial activity of the biofertilizer was studied using isothermal calorimetry. The results showed that the microbial community of the biofertilizer changed distinctly through a necessary initial nitrification process, and that the most abundant genus was Mycobacterium. Deliberate contaminations with 5 log₁₀ CFU mL⁻¹ of either S. enterica or L. monocytogenes in the nitrified biofertilizer were no longer detectable with selective plating after 48 h of incubation at 20 °C. Selective plating for B. cereus revealed that the biofertilizer contained low levels (∼10 CFU mL⁻¹) of the bacterium, and an inoculation of 5 log₁₀ CFU mL⁻¹B. cereus decreased to these levels within 24 h of incubation at 20 °C. Analysis of the microbial activity of the biofertilizer indicated that the biofertilizer does not seem to support microbial activity without the addition of an external nutrient source that contains an accessible carbon source and trace elements. The type of biofertilizer investigated in this study is thus regarded as microbiologically safe for use in hydroponic cultivation. The constant presence of viable B. cereus, however, emphasizes the fundamental importance of continuous risk assessment in case of any modifications or supplementations of the biofertilizer, since it clearly can act as a reservoir for bacterial endospores.
Keywords	Bacillus cereus ; Listeria monocytogenes ; Mycobacterium ; Salmonella enterica ; arable soils ; bacteria ; biofertilizers ; biogas ; calorimetry ; carbon ; digestion ; endospores ; food production ; food safety ; food waste ; genes ; hydroponics ; liquids ; microbial activity ; microbial communities ; mineral fertilizers ; nitrification ; risk assessment
Language	English
Dates of publication	2022-0120
Publishing place	Elsevier Ltd
Document type	Article
ISSN	0959-6526
DOI	10.1016/j.jclepro.2021.130239
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: New insights into PKC family affairs: three novel phosphorylation sites in PKCepsilon and at least one is regulated by PKCalpha.

Larsson, Christer

The Biochemical journal

2008 Volume 411, Issue 2, Page(s) e15–6

Abstract: PKCepsilon (protein kinase Cepsilon) is a serine/threonine kinase, and a member of the PKC family of isoforms. The different PKC isoforms regulate many cellular processes of importance for disease. It is therefore desirable to obtain tools to ... ...

Abstract	PKCepsilon (protein kinase Cepsilon) is a serine/threonine kinase, and a member of the PKC family of isoforms. The different PKC isoforms regulate many cellular processes of importance for disease. It is therefore desirable to obtain tools to specifically modulate the activity of the individual isoforms and to develop markers of PKC activity. The paper by Durgan et al. in this issue of the Biochemical Journal has taken us some steps further towards these goals. In the paper they identify three previously unknown phosphorylation sites in PKCepsilon. All of them are specific for the epsilon isoform, evolutionarily conserved and tightly regulated. The phosphorylation of one site is critical for the binding of PKCepsilon to 14-3-3beta, suggesting it is of functional importance. The results provide important novel findings that uncover new aspects of PKCepsilon regulation and reveal new possibilities for detecting PKCepsilon activity in situ.
MeSH term(s)	Phosphorylation ; Protein Kinase C-alpha/classification ; Protein Kinase C-alpha/metabolism ; Protein Kinase C-epsilon/classification ; Protein Kinase C-epsilon/genetics ; Protein Kinase C-epsilon/metabolism
Chemical Substances	Protein Kinase C-alpha (EC 2.7.11.13) ; Protein Kinase C-epsilon (EC 2.7.11.13)
Language	English
Publishing date	2008-04-15
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	2969-5
ISSN	1470-8728 ; 0006-2936 ; 0306-3275 ; 0264-6021
ISSN (online)	1470-8728
ISSN	0006-2936 ; 0306-3275 ; 0264-6021
DOI	10.1042/BJ20080373
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Book ; Thesis: Liver and lung manifestations in alpha 1 antitrypsin deficiency

Larsson, Christer

1979

Author's details	av Christer Larsson
Language	English
Size	35 S.
Publishing country	Sweden
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Lund, Univ., Diss., 1979
HBZ-ID	HT002263869
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