Vol. 14 No. 1 March 2009

DOI: 10.2478/s11658-008-0024-7 Volume 14 (2009) pp 1-22
Title THE INTERACTOME: PREDICTING THE PROTEIN-PROTEIN INTERACTIONS IN CELLS
Authors Dariusz Plewczyński* and Krzysztof Ginalski
Abstract The term Interactome describes the set of all molecular interactions in cells, especially in the context of protein-protein interactions. These interactions are crucial for most cellular processes, so the full representation of the interaction repertoire is needed to understand the cell molecular machinery at the system biology level. In this short review, we compare various methods for predicting protein-protein interactions using sequence and structure information. The ultimate goal of those approaches is to present the complete methodology for the automatic selection of interaction partners using their amino acid sequences and/or three dimensional structures, if known. Apart from a description of each method, details of the software or web interface needed for high throughput prediction on the whole genome scale are also provided. The proposed validation of the theoretical methods using experimental data would be a better assessment of their accuracy.
Keywords Protein-protein interactions, Protein complexes, Docking, PDB Database, Interactome, Protein interaction networks, Physical protein interactions
Address and Contact Information Interdisciplinary Centre for Mathematical and Computational Modelling, University of Warsaw, Pawińskiego 5a, 02-106 Warsaw, Poland
*Author for correspondence; e-mail: D.Plewczynski@icm.edu.pl, tel.: (+48 22) 554-08-39, f ax: (+48 22) 554-40-801
[Rozmiar: 1332 bajtów]

DOI: 10.2478/s11658-008-0031-8 Volume 14 (2009) pp 23-34
Title THE EFFECTS OF SUPEROXIDE DISMUTASE KNOCKOUT ON THE OXIDATIVE STRESS PARAMETERS AND SURVIVAL OF MOUSE ERYTHROCYTES
Authors Agnieszka Grzelak1, Marcin Kruszewski2, Ewa Macierzyńska1, Łukasz Piotrowski1*, Łukasz Pułaski1,3, Błażej Rychlik1 and Grzegorz Bartosz1,4
Abstract The erythrocytes of 12-month old Sod1-/- mice showed an increased level of reactive oxygen species (ROS), as estimated by the degree of dihydroethidine and dihydrorhodamine oxidation, and the increased level of Heinz bodies. No indices of severe oxidative stress were found in the red blood cells and blood plasma of Sod1-/- mice as judged from the lack of significant changes in the levels of erythrocyte and plasma glutathione, plasma protein thiol and carbonyl groups and thiobarbituric-acid reactive substances in the blood plasma. However, a decreased erythrocyte lifespan, increased reticulocyte count and splenomegaly were noted, indicating the importance of superoxide dismutase for maintaining erythrocyte viability. The levels of erythrocyte ROS and Heinz bodies and the reticulocyte count were indistinguishable in Sod1+/+ and Sod1+/- mice, suggesting that a superoxide dismutase activity decrease to half of its normal value may be sufficient to secure the protective effects of the enzyme.
Keywords Superoxide dismutase, Erythrocyte, Red blood cell, Reactive oxygen species, Oxidative stress, Heinz bodies, Acetylcholinesterase
Address and Contact Information 1Department of Molecular Biophysics, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland,
2Department of Radiobiology and Health Protection, Institute of Nuclear Chemistry and Technology, Dorodna 16, 31-159 Warsaw, Poland,
3Laboratory of Transcriptional Regulation, Centre of Medical Biology, Polish Academy of Sciences, Lodowa 106, 93-232 Łódź, Poland,
4Department of Biochemistry and Cell Biology, University of Rzeszów, Cegielniana 12, 35-959 Rzeszów, Poland
* Author for correspondence: e-mail: lu kaszp@biol.uni.lodz.pl, tel./fax: +48 42 6354476
[Rozmiar: 1332 bajtów]

DOI: 10.2478/s11658-008-0032-7 Volume 14 (2009) pp 35-45
Title 31P MRS ANALYSIS OF THE PHOSPHOLIPID COMPOSITION OF THE PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) AND BONE MARROW MONONUCLEAR CELLS (BMMC) OF PATIENTS WITH ACUTE LEUKEMIA (AL)
Authors Małgorzata Kuliszkiewicz-Janus1, 2*, Mariusz Adam Tuz1, Marek Kiełbiński1, Bożena JaĄwiec1, Joanna Niedoba1 and Stanisław Baczyński3
Abstract The aim of this study was to evaluate the phospholipid concentration in acute leukemia (AL) blast cells from peripheral blood (PBMC) and bone marrow (BMMC). In vitro 31P Nuclear Magnetic Resonance Spectroscopy (31P MRS) was used. The integral intensities of the resonant peaks and the phospholipid concentrations in PBMC and BMMC were analyzed. Differences in the phospholipid concentrations in cells from myeloblastic or lymphoblastic lines were also evaluated. This investigation was carried out on phospholipid extracts from PBMC and BMMC from 15 healthy volunteers and 77 patients with AL (samples taken at the moment of diagnosis). A significant decrease in sphingomyelin (SM) and phosphtidylserine (PS) was observed in the PBMC of patients with AL relative to the results for the healthy volunteers. For ALL, we found a significant decrease in the concentration of phosphatidylcholine plasmalogen (CPLAS), SM, PI+PE (phosphatidylinositol + phosphatidylethanolamine) and PS in comparison with the results for healthy volunteers and patients with AML. Experiments with BMMC cells revealed a significant decrease in the concentration of CPLAS, SM, PI+PE, and PS in ALL relative to AML. Additionally, a significant decrease in phosphatidylcholine (PC) concentration was observed in ALL compared to AML. If the phospholipid extracts were taken simultaneously from the same patient, there were no significant differences in the integral intensities and phospholipid concentrations between PBMC and BMMC.
Keywords Acute leukemia, 31P MRS, Phospholipids
Address and Contact Information 1Department of Haematology and Transplantology, Wrocław Medical University, Wrocław, Poland,
2Academic Centre for the Biotechnology of Lipid Aggregates, Wrocław, Poland,
3Faculty of Chemistry, University of Wrocław, Wrocław, Poland
* Author for correspondence: mkj@hemat.am.wroc.pl
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DOI: 10.2478/s11658-008-0033-6 Volume 14 (2009) pp 46-56
Title THE GTPASE DOMAIN OF Galphao CONTRIBUTES TO THE FUNCTIONAL INTERACTION OF Galphao WITH THE PROMYELOCYTIC LEUKEMIA ZINC FINGER PROTEIN
Authors Jung Hee Won1 and Sung Ho Ghil*
Abstract Go, one of the most abundant heterotrimeric G proteins in the brain, is classified as a member of the Gi/Go family based on its homology to Gi proteins. Recently, we identified promyelocytic leukemia zinc finger protein (PLZF) as a candidate downstream effector for the alpha subunit of Go (Gαo). Activated Gαo interacts with PLZF and augments its function as a repressor of transcription and cell growth. G protein-coupled receptor-mediated Gαo activation also enhanced PLZF function. In this study, we determined that the GTPase domain of Gαo contributes to Gαo:PLZF interaction. We also showed that the Gαo GTPase domain is important in modulating the function of PLZF. This data indicates that the GTPase domain of Gαo may be necessary for the functional interaction of Gαo with PLZF.
Keywords Cell growth, Differentiation, Domain, G protein
Address and Contact Information Department of Life Science, Kyonggi University, Suwon 443-760, South Korea
* Author for correspondence: e-mail: shghil@kyonggi.ac.kr, tel.: 82-31-249-9646, fax: 82-31-249-9646
1Current address: ViroMed Co. Ltd., 1510-8 Bongcheon-dong, Gwanak-gu, Seoul, 1 51-818, South Korea
[Rozmiar: 1332 bajtów]

DOI: 10.2478/s11658-008-0035-4 Volume 14 (2009) pp 57-69
Title THE INTERACTION BETWEEN L1-TYPE PROTEINS AND ANKYRINS - A MASTER SWITCH FOR L1-TYPE CAM FUNCTION #
Authors Michael Hortsch1*, Kakanahalli Nagaraj1,2 and Tanja A. Godenschwege3
Abstract L1-type cell adhesion molecules (CAMs) are important mediators of neural differentiation, including axonal outgrowth and pathfinding and also of synapse formation and maintenance. In addition, their interactions with cytoskeletal components are highly conserved and regulated. How these different aspects of CAM functionality relate to each other is not well understood. Based on results from our and other laboratories we propose that ankyrin-binding to L1-type CAMs provides a master switch. The interaction with ankyrins directs L1-type adhesive proteins into different functional contexts, either ankyrin-independent functions, such as neurite outgrowth and axonal pathfinding or into ankyrin-dependent functions, such as L1’s role at axon initial segments (AIS), paranodal regions, synapses and in dendrites.
Keywords Cell adhesion, Ankyrins, Membrane skeleton, Tyrosine phosphorylation, Neurite outgrowth, Neuromuscular junction, Synapse, Synaptogenesis, Drosophila
Address and Contact Information 1Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI 48109, USA,
2present address: Department of Applied Zoology, Kuvempu University, Shankaraghatta, Shimoga, India,
3Florida Atlantic University, Department of Biological Sciences, Boca Raton, FL 33431, USA
# The content of this Mini review was first presented in a shortened form at the 12th Mejbaum-Katzenellenbogen Seminar “Membrane Skeleton. Recent Advances and Future Research Directions”, June 15-18, 2008, Zakopane, Poland
* Author for correspondence; e-mail: hortsch@umich.edu, tel.: (734) 647 2720, fax: (734) 7 63 1166
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DOI: 10.2478/s11658-008-0034-5 Volume 14 (2009) pp 70-89
Title CORRELATION BETWEEN THE LEVELS OF SURVIVIN AND SURVIVIN PROMOTER-DRIVEN GENE EXPRESSION IN CANCER AND NON-CANCER CELLS
Authors Krystyna Konopka*, Christopher Spain, Allison Yen, Nathan Overlid, Senait Gebremedhin and Nejat Duzgunes
Abstract Survivin, a member of the inhibitor of apoptosis (IAP) protein family, is associated with malignant transformation and is over-expressed in most human tumors. Using lipoplex-mediated transfection, we evaluated the activity of the reporter enzyme, luciferase, expressed from plasmids encoding the enzyme under the control of either the cytomegalovirus (CMV) or survivin promoters, in tumor- and non-tumor-derived human and murine cells. We also examined whether there is a correlation between the survivin promoter-driven expression of luciferase and the level of endogenous survivin. Human cancer cells (HeLa, KB, HSC-3, H357, H376, H413), oral keratinocytes, GMSM-K, and chemically immortalized human mammary cells, 184A-1, were transfected with Metafectene at 2 µl/1 µg DNA. Murine squamous cell carcinoma cells, SCCVII, mouse embryonic fibroblasts, NIH-3T3, and murine immortalized mammary cells, NMuMG, were transfected with Metafectene PRO at 2 µl/1 µg DNA. The expression of luciferase was driven by the CMV promoter (pCMV.Luc), the human survivin promoter (pSRVN.Luc-1430), or the murine survivin promoters (pSRVN.Luc-1342 and pSRVN.Luc-194). Luciferase activity was measured, using the Luciferase Assay System and expressed as relative light units (RLU) per ml of cell lysate or per mg of protein. The level of survivin in the lysates of human cells was determined by ELISA and expressed as ng survivin/mg protein. In all cell lines, significantly higher luciferase activity was driven by the CMV promoter than by survivin promoters. The expression of luciferase driven by the CMV and survivin promoters in murine cells was much higher than that in human cells. The cells displayed very different susceptibilities to transfection; nevertheless, high CMV-driven luciferase activity appeared to correlate with high survivin-promoter driven luciferase expression. The survivin concentration in lysates of cancer cells ranged from 5.8 ± 2.3 to 24.3 ± 2.9 ng/mg protein (mean, 13.7 ng/mg). Surprisingly, elevated survivin protein was determined in lysates of non-tumor-derived cells. Survivin levels for GMSM-K and 184A-1 cells, were 16.7 ± 8.7 and 13.5 ± 6.2 ng/mg protein, respectively. The expression of endogenous survivin did not correlate with the level of survivin promoter-driven transgene activity in the same cells. The expression of survivin by non-tumorigenic, transformed cell lines may be necessary for their proliferative activity. The level of survivin promoter-driven gene expression achieved via liposomal vectors in OSCC cells was too low to be useful in cancer-cell specific gene therapy.
Keywords Transfection, Survivin, Metafectene, Metafectene PRO, Survivin promoter, Non-cancer cells, CMV promoter, Oral squamous cell carcinoma cells
Address and Contact Information Department of Microbiology, University of the Pacific, Arthur A. Dugoni School of Dentistry, San Francisco, CA 94115, USA
* Author for correspondence: e-mail: kkonopka@pacific.edu
[Rozmiar: 1332 bajtów]

DOI: 10.2478/s11658-008-0036-3 Volume 14 (2009) pp 90-99
Title THE CARNITINE ACETYLTRANSFERASE GENE (CRAT): A CHARACTERIZATION OF PORCINE TRANSCRIPTS WITH INSIGHTS INTO THE 5’-END VARIANTS OF MAMMALIAN TRANSCRIPTS AND THEIR POSSIBLE
Authors Annie Robic*, Thomas Faraut, Laurence Liaubet and Denis Milan
Abstract Carnitine acetyltransferase (CRAT) is an important enzyme for energy homeostasis and fat metabolism. We characterized the predicted full length cDNA sequence of the porcine CRAT gene. Its structure is very similar to that in humans with respect to the size and organization of the 14 exons. We demonstrated the existence of a porcine alternative transcript resulting from a partial intron-retention at the 5’ end of exon 2. To perform a comparison of the 5’ end variants of the mammalian CRAT gene, we analyzed the Genbank data, and here we propose a new 5’ variant for dog, rat and mouse. In contrast to other mammals where this variant encodes a shorter protein (-21 aa in human, mouse and rat, and -14 aa in dog), the pig variant encodes for a longer protein (+18 aa). In all mammalian species, variant 1 has a high probability of a preferential mitochondrial sub-cellular localization. Nevertheless, it is not evident, in particular in porcine and dog species, that the second variant is associated with a different sub-cellular specificity.
Keywords Pig, CRAT, mRNA, Alternative splicing, Mammals, Fat metabolism, Leader peptide
Address and Contact Information Institut National de la Recherche Agronomique (INRA), Laboratoire de Génétique Cellulaire, UMR 444, BP52627, 31326 Castanet Tolosan Cedex, France
* Author for correspondence: e-mail: annie.robic@toulouse.inra.fr, tel.: +33 5 61 28 51 15, f ax: +33 5 61 28 53 08
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DOI: 10.2478/s11658-008-0038-1 Volume 14 (2009) pp 100-112
Title HOMING OF ANNEXIN-LABELED STEM CELLS TO APOPTOTIC CELLS
Authors Argyrios Gerasimou1#, Roberta Ramella2#, Alessia Brero2#, Ombretta Boero2, Imad Sheiban1, Renzo Levi2 and Maria Pia Gallo2*
Abstract Ischemic diseases are characterized by the presence of pro-apoptotic stimuli, which initiate a cascade of processes that lead to cell injury and death. Several molecules and events represent detectable indicators of the different stages of apoptosis. Among these indicators is phosphatidylserine (PS) translocation from the inner to the outer leaflet of the plasma membrane, which can be detected by annexinV (ANXA5) conjugation. This is a widely used in vivo and in vitro assay marking the early stages of apoptosis. We report here on an original method that employs PS-ANXA5 conjugation to target stem cells to apoptotic cells. Mesenchymal stem cells (MSCs) from GFP-positive transgenic rats were biotinylated on membrane surfaces with sulfosuccinimidyl- 6-(biotinamido) hexanoate (sulfo-NHS-LC-biot) and then bound to avidin. The avidin-biotinylated MSCs were labeled with biotin conjugated ANXA5. Bovine aortic endothelial cells (BAE-1 cells) were exposed to UVC to induce caspasedependent apoptosis. Finally, we tested the ability of ANXA5-labeled MSCs to bind BAE-1 apoptotic cells: suspended ANXA5-labeled MSCs were seeded for 1 hour on a monolayer of UV-treated or control BAE-1 cells. After washing, the number of MSCs bound to BAE-1 cells was evaluated by confocal microscopy. Statistical analysis demonstrated a significant increase in the number of MSCs tagged to apoptotic BAE-1 cells. Therefore, stem cell ANXA5 tagging via biotin-avidin bridges could be a straightforward method of improving homing to apoptotic tissues.
Keywords Stem cell, Apoptosis, Homing, Annexin
Address and Contact Information 1Interventional Cardiology, Division of Cardiology, University of Torino, Torino, Italy,
2Department of Animal and Human Biology, University of Torino, Torino, Italy
# A. Gerasimou, R. Ramella and A. Brero contributed equally to this paper.
* Author for correspondence: Maria Pia Gallo, Department of Animal and Human Biology, University of Torino, via Accademia Albertina 13, 10123 Torino. e-mail: mariapia.gallo@unito.i t, tel.: +3911 670 4671, fax: +3911 670 4508
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DOI: 10.2478/s11658-008-0037-2 Volume 14 (2009) pp 113-127
Title DOXORUBICIN-TRANSFERRIN CONJUGATE SELECTIVELY OVERCOMES MULTIDRUG RESISTANCE IN LEUKAEMIA CELLS
Authors Dorota Łubgan1,*, Zofia Jóźwiak2, Gerhard G. Grabenbauer1 and Luitpold V. R. Distel1
Abstract Neoplastic cells frequently have an increased number of transferrin receptors. Coupling transferrin to an anti-neoplastic drug has the potential to overcome multidrug resistance (MDR). The purpose of this study was to examine the distribution and action of doxorubicin-transferrin conjugate (DOXTRF) in a leukaemia cell line (HL60), a multidrug-resistant leukaemia cell line (HL60ADR) and a normal tissue cell line (human fibroblasts). The intracellular accumulation of DOX and DOX-TRF was monitored by direct fluorescence. More DOX-TRF than free DOX was delivered to the tumour cells, and consecutively the levels of DNA double-strand breaks and apoptosis increased even in the multidrug-resistant cell line. In the normal tissue cell line, DOX-TRF did not accumulate, and therefore, the levels of DNA double-strand breaks and apoptosis did not increase. Cell viability was determined using the MTT assay. The IC50 for DOX-TRF was lower than the IC50 value for the free drug in both leukaemia cell lines. The IC50 values for the HL60 cells were 0.08 µM for DOX and 0.02 µM for DOX-TRF. The IC50 values for HL60ADR cells were 7 µM for DOX and 0.035 µM for DOX-TRF. In conclusion, DOX-TRF was able to overcome MDR in the leukaemia cell lines while having only a very limited effect on normal tissue cells.
Keywords Doxorubicin-transferrin, Promyelocytic leukaemia, Apoptosis, DNA double-strand breaks, Multidrug resistance
Address and Contact Information 1Department of Radiation Oncology, Friedrich-Alexander-University Erlangen- Nuremberg, Universitätsstr. 27, D-91054 Erlangen, Germany,
2Department of Thermobiology, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland
* Author for correspondence: e-mail: Dorota.Lubgan@uk-erlangen.de, tel.: +49 9131 853 2 312, fax: +49 9131 853 9335
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DOI: 10.2478/s11658-008-0039-0 Volume 14 (2009) pp 128-138
Title GALECTIN-1 EXPRESSION IN INNERVATED AND DENERVATED SKELETAL MUSCLE
Authors Anna Svensson* and Sven Tagerud
Abstract Galectin-1 is a soluble carbohydrate-binding protein with a particularly high expression in skeletal muscle. Galectin-1 has been implicated in skeletal muscle development and in adult muscle regeneration, but also in the degeneration of neuronal processes and/or in peripheral nerve regeneration. Exogenously supplied oxidized galectin-1, which lacks carbohydrate-binding properties, has been shown to promote neurite outgrowth after sciatic nerve sectioning. In this study, we compared the expression of galectin-1 mRNA and immunoreactivity in innervated and denervated mouse and rat hind-limb and hemidiaphragm muscles. The results show that galectin-1 mRNA expression and immunoreactivity are up-regulated following denervation. The galectin-1 mRNA is expressed in the extrasynaptic and perisynaptic regions of the muscle, and its immunoreactivity can be detected in both regions by Western blot analysis. The results are compatible with a role for galectin-1 in facilitating reinnervation of denervated skeletal muscle.
Keywords Galectin-1, Skeletal muscle, Denervation
Address and Contact Information School of Pure and Applied Natural Sciences, University of Kalmar, SE-391 82 Kalmar, Sweden
* Author for correspondence; e-mail: anna.svensson@hik.se, tel.: +46-480-446264, fax: + 46-480-446262
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DOI: 10.2478/s11658-008-0041-6 Volume 14 (2009) pp 139-152
Title ORAL CYCLOSPORINE A – THE CURRENT PICTURE OF ITS LIPOSOMAL AND OTHER DELIVERY SYSTEMS
Authors Aleksander Czogalla*
Abstract The discovery of cyclosporine A was a milestone in organ transplantation and the treatment of autoimmune diseases. However, developing an efficient oral delivery system for this drug is complicated by its poor biopharmaceutical characteristics (low solubility and permeability) and the need to carefully monitor its levels in the blood. Current research is exploring various approaches, including those based on emulsions, microspheres, nanoparticles, and liposomes. Although progress has been made, none of the formulations is flawless. This review is a brief description of the main pharmaceutical systems and devices that have been described for the oral delivery of cyclosporine A in the context of the physicochemical properties of the drug and the character of its interactions with lipid membranes.
Keywords Cyclosporine A, Physicochemical properties, Oral drug delivery, Liposomes, Nanoparticles
Address and Contact Information Research and Development Centre Novasome Sp. z o.o., ul. Olsztyńska 5, 51-423 Wrocław, Poland
*Correspondence and current address: Pharmaceutical Production Company Hasco-Lek S.A., ul. Żmigrodzka 242 E, 51-131 Wrocław, Poland, e-mail: a.czogalla@hasco-lek.pl, tel.: +48- 7 1-327-19-88, fax: +48-71-352-95-48
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DOI: 10.2478/s11658-008-0040-7 Volume 14 (2009) pp 153-174
Title REGULATOR OF G-PROTEIN SIGNALLING EXPRESSION AND FUNCTION IN OVARIAN CANCER CELL LINES
Authors Jillian H. Hurst, Nisha Mendpara and Shelley B. Hooks*
Abstract Regulator of G-protein signalling (RGS) proteins critically regulate signalling cascades initiated by G-protein coupled receptors (GPCRs) by accelerating the deactivation of heterotrimeric G-proteins. Lysophosphatidic acid (LPA) is the predominant growth factor that drives the progression of ovarian cancer by activating specific GPCRs and G-proteins expressed in ovarian cancer cells. We have recently reported that RGS proteins endogenously expressed in SKOV-3 ovarian cancer cells dramatically attenuate LPA stimulated cell signalling. The goal of this study was twofold: first, to identify candidate RGS proteins expressed in SKOV-3 cells that may account for the reported negative regulation of G-protein signalling, and second, to determine if these RGS protein transcripts are differentially expressed among commonly utilized ovarian cancer cell lines and non-cancerous ovarian cell lines. Reverse transcriptase-PCR was performed to determine transcript expression of 22 major RGS subtypes in RNA isolated from SKOV-3, OVCAR-3 and Caov-3 ovarian cancer cell lines and non-cancerous immortalized ovarian surface epithelial (IOSE) cells. Fifteen RGS transcripts were detected in SKOV-3 cell lines. To compare the relative expression levels in these cell lines, quantitative real time RT-PCR was performed on select transcripts. RGS19/GAIP was expressed at similar levels in all four cell lines, while RGS2 transcript was detected at levels slightly lower in ovarian cancer cells as compared to IOSE cells. RGS4 and RGS6 transcripts were expressed at dramatically different levels in ovarian cancer cell lines as compared to IOSE cells. RGS4 transcript was detected in IOSE at levels several thousand fold higher than its expression level in ovarian cancer cells lines, while RGS6 transcript was expressed fivefold higher in SKOV-3 cells as compared to IOSE cells, and over a thousand fold higher in OVCAR-3 and Caov-3 cells as compared to IOSE cells. Functional studies of RGS 2, 6, and 19/GAIP were performed by measuring their effects on LPA stimulated production of inositol phosphates. In COS-7 cells expressing individual exogenous LPA receptors, RGS2 and RSG19/GAIP attenuated signalling initiated by LPA1, LPA2, or LPA3, while RGS6 only inhibited signalling initiated by LPA2 receptors. In SKOV-3 ovarian cancer cells, RGS2 but not RGS6 or RGS19/GAIP, inhibited LPA stimulated inositol phosphate production. In contrast, in CAOV-3 cells RGS19/GAIP strongly attenuated LPA signalling. Thus, multiple RGS proteins are expressed at significantly different levels in cells derived from cancerous and normal ovarian cells and at least two candidate RGS transcripts have been identified to account for the reported regulation of LPA signalling pathways in ovarian cancer cells.
Keywords Regulator of G-protein signalling (RGS) proteins, Ovarian cancer, SKOV-3, OVCAR-3, Caov-3, IOSE, RT-PCR
Address and Contact Information Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens GA USA 30602
* Author for correspondence: 377 Wilson Pharmacy Building, 250 West Green Street, Athens, GA 30602-2352, USA; e-mail: shooks@rx.uga.edu, tel.: 706-542-2189, fax: 706- 5 42-5358
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