المؤلفون: Sikkeland J; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, 0310 Oslo, Norway., Lindstad T; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway., Nenseth HZ; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway., Dezitter X; Plateforme de Binding et de Biologie Moléculaire, Institut de Chimie Pharmaceutique Albert Lespagnol, Faculté des Sciences Pharmaceutiques et Biologiques - Université de Lille, F-59006 Lille, France., Qu S; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway., Muhumed RM; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway., Ertunc ME; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway; Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard TH Chan School of Public Health, Boston, MA 02115, USA., Gregor MF; Department of Genetics and Complex Diseases and Sabri Ülker Center, Harvard TH Chan School of Public Health, Boston, MA 02115, USA., Saatcioglu F; Department of Biosciences, University of Oslo, Postboks 1066 Blindern, 0316 Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, 0310 Oslo, Norway. Electronic address: fahris@ibv.uio.no.

المصدر: Metabolism: clinical and experimental [Metabolism] 2019 Apr; Vol. 93, pp. 75-85. Date of Electronic Publication: 2019 Jan 30.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Inc Country of Publication: United States NLM ID: 0375267 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-8600 (Electronic) Linking ISSN: 00260495 NLM ISO Abbreviation: Metabolism Subsets: MEDLINE

مواضيع طبية MeSH: Endoplasmic Reticulum Stress*/drug effects, Adipocytes/*metabolism , Inflammation/*metabolism , Membrane Proteins/*metabolism, Adipocytes/pathology ; Animals ; Cells, Cultured ; Inflammation/chemically induced ; Membrane Proteins/analysis ; Membrane Proteins/deficiency ; Mice ; RNA, Messenger/analysis ; Thapsigargin/pharmacology ; Tumor Necrosis Factor-alpha/pharmacology

مستخلص: Background: Chronic ER stress and dysfunction is a hallmark of obesity and a critical contributor to metaflammation, abnormal hormone action and altered substrate metabolism in metabolic tissues, such as liver and adipocytes. Lack of STAMP2 in lean mice induces inflammation and insulin resistance on a regular diet, and it is dysregulated in the adipose tissue of obese mice and humans. We hypothesized that the regulation of STAMP2 is disrupted by ER stress.
Methods: 3T3-L1 and MEF adipocytes were treated with ER stress inducers thapsigargin and tunicamycin, and inflammation inducer TNFα. The treatments effect on STAMP2 expression and enzymatic function was assessed. In addition, 3T3-L1 adipocytes and HEK cells were utilized for Stamp2 promoter activity investigation performed with luciferase and ChIP assays.
Results: ER stress significantly reduced both STAMP2 mRNA and protein expression in cultured adipocytes whereas TNFα had the opposite effect. Concomitant with loss of STAMP2 expression during ER stress, intracellular localization of STAMP2 was altered and total iron reductase activity was reduced. Stamp2 promoter analysis by reporter assays and chromatin immunoprecipitation, showed that induction of ER stress disrupts C/EBPα-mediated STAMP2 expression.
Conclusion: These data suggest a clear link between ER stress and quantitative and functional STAMP2-deficiency.
(Copyright © 2019 Elsevier Inc. All rights reserved.)

المؤلفون: Sikkeland J; Department of Biosciences, University of Oslo, Oslo, Norway., Sheng X; Department of Biosciences, University of Oslo, Oslo, Norway., Jin Y; Department of Biosciences, University of Oslo, Oslo, Norway., Saatcioglu F; Department of Biosciences, University of Oslo, Oslo, Norway; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway. Electronic address: fahris@ibv.uio.no.

المصدر: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2016 Apr 15; Vol. 425, pp. 26-36. Date of Electronic Publication: 2016 Feb 18.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: North Holland Publishing Country of Publication: Ireland NLM ID: 7500844 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8057 (Electronic) Linking ISSN: 03037207 NLM ISO Abbreviation: Mol Cell Endocrinol Subsets: MEDLINE

مواضيع طبية MeSH: Membrane Proteins/*metabolism , Neoplasm Proteins/*metabolism , Oncogene Proteins/*metabolism , Oxidoreductases/*metabolism, Animals ; Cell Cycle Proteins ; Cell Differentiation ; Gene Expression Regulation ; Humans ; Inflammation/metabolism ; Membrane Proteins/chemistry ; Membrane Proteins/genetics ; Metabolic Diseases/metabolism ; Neoplasm Proteins/chemistry ; Neoplasm Proteins/genetics ; Neoplasms/metabolism ; Oncogene Proteins/chemistry ; Oncogene Proteins/genetics ; Oxidoreductases/chemistry ; Oxidoreductases/genetics ; Tissue Distribution

مستخلص: The six transmembrane protein of prostate (STAMP) proteins, also known as six transmembrane epithelial antigen of prostate (STEAPs), comprises three members: STAMP1-3. Their expression is regulated by a variety of stimuli, including hormones and cytokines, in varied settings and tissues with important roles in secretion and cell differentiation. In addition, they are implicated in metabolic and inflammatory diseases and cancer. Here, we review the current knowledge on the role of STAMPs in both physiological and pathological states.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

المؤلفون: Jin Y; Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway., Wang L; Department of Biosciences, University of Oslo, Oslo, Norway., Qu S; Department of Biosciences, University of Oslo, Oslo, Norway., Sheng X; Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway., Kristian A; Department of Tumor Biology, Oslo University Hospital, Oslo, Norway., Mælandsmo GM; Department of Tumor Biology, Oslo University Hospital, Oslo, Norway., Pällmann N; Department of Biosciences, University of Oslo, Oslo, Norway., Yuca E; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Tekedereli I; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Gorgulu K; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Alpay N; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Sood A; Gynecological Oncology, MD Anderson Cancer Center, Houston, TX, USA., Lopez-Berestein G; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Fazli L; The Vancouver Prostate Centre, Vancouver, BC, Canada., Rennie P; The Vancouver Prostate Centre, Vancouver, BC, Canada., Risberg B; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Division of Pathology, Oslo University Hospital, Oslo, Norway Division of Surgery, Oslo University Hospital, Oslo, Norway., Wæhre H; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Division of Pathology, Oslo University Hospital, Oslo, Norway Division of Surgery, Oslo University Hospital, Oslo, Norway Center for Cancer Biomedicine, University of Oslo, Oslo, Norway., Danielsen HE; Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway Center for Cancer Biomedicine, University of Oslo, Oslo, Norway Department of Informatics, University of Oslo, Oslo, Norway., Ozpolat B; Department of Experimental Therapeutics, MD Anderson Cancer Center, Houston, TX, USA., Saatcioglu F; Department of Biosciences, University of Oslo, Oslo, Norway Institute for Cancer Genetics and Informatics, Oslo University Hospital, Oslo, Norway fahris@ibv.uio.no.

المصدر: EMBO molecular medicine [EMBO Mol Med] 2015 Mar; Vol. 7 (3), pp. 315-31.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101487380 Publication Model: Print Cited Medium: Internet ISSN: 1757-4684 (Electronic) Linking ISSN: 17574676 NLM ISO Abbreviation: EMBO Mol Med Subsets: MEDLINE

مواضيع طبية MeSH: Oxidative Stress*, Membrane Proteins/*metabolism , Oxidoreductases/*metabolism , Prostatic Neoplasms/*pathology, Activating Transcription Factor 4/metabolism ; Animals ; Cell Line, Tumor ; Disease Models, Animal ; FMN Reductase/genetics ; FMN Reductase/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Humans ; Male ; Membrane Proteins/genetics ; Mice ; Oxidoreductases/genetics ; Prostatic Neoplasms/genetics ; Reactive Oxygen Species ; Transplantation, Heterologous

مستخلص: The six transmembrane protein of prostate 2 (STAMP2) is an androgen-regulated gene whose mRNA expression is increased in prostate cancer (PCa). Here, we show that STAMP2 protein expression is increased in human PCa compared with benign prostate that is also correlated with tumor grade and treatment response. We also show that STAMP2 significantly increased reactive oxygen species (ROS) in PCa cells through its iron reductase activity which also depleted NADPH levels. Knockdown of STAMP2 expression in PCa cells inhibited proliferation, colony formation, and anchorage-independent growth, and significantly increased apoptosis. Furthermore, STAMP2 effects were, at least in part, mediated by activating transcription factor 4 (ATF4), whose expression is regulated by ROS. Consistent with in vitro findings, silencing STAMP2 significantly inhibited PCa xenograft growth in mice. Finally, therapeutic silencing of STAMP2 by systemically administered nanoliposomal siRNA profoundly inhibited tumor growth in two established preclinical PCa models in mice. These data suggest that STAMP2 is required for PCa progression and thus may serve as a novel therapeutic target.
(© 2015 The Authors. Published under the terms of the CC BY 4.0 license.)

المؤلفون: Sikkeland J; Department of Biosciences, University of Oslo, Postboks, Oslo, Norway., Saatcioglu F

المصدر: PloS one [PLoS One] 2013 Jul 10; Vol. 8 (7), pp. e68249. Date of Electronic Publication: 2013 Jul 10 (Print Publication: 2013).

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE

مواضيع طبية MeSH: Adipocytes/*physiology , Adipogenesis/*genetics , Antigens, Neoplasm/*genetics , Cell Differentiation/*genetics , Membrane Proteins/*genetics, 3T3-L1 Cells ; Adipocytes/drug effects ; Adipocytes/metabolism ; Adipogenesis/drug effects ; Animals ; Antigens, Neoplasm/metabolism ; Cell Differentiation/drug effects ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/physiology ; Gene Knockdown Techniques ; Membrane Proteins/antagonists & inhibitors ; Membrane Proteins/metabolism ; Mice ; Multigene Family/genetics ; RNA, Small Interfering/pharmacology

مستخلص: Six transmembrane protein of prostate (Stamp) proteins play an important role in prostate cancer cell growth. Recently, we found that Stamp2 has a critical role in the integration of inflammatory and metabolic signals in adipose tissue where it is highly expressed and regulated by nutritional and metabolic cues. In this study, we show that all Stamp family members are differentially regulated during adipogenesis: whereas Stamp1 expression is significantly decreased upon differentiation, Stamp2 expression is increased. In contrast, Stamp3 expression is modestly changed in adipocytes compared to preadipocytes, and has a biphasic expression pattern during the course of differentiation. Suppression of Stamp1 or Stamp2 expression both led to inhibition of 3T3-L1 differentiation in concert with diminished expression of the key regulators of adipogenesis - CCAAT/enhancer binding protein alpha (C/ebpα) and peroxisome proliferator-activated receptor gamma (Pparγ). Upon Stamp1 knockdown, mitotic clonal expansion was also inhibited. In contrast, Stamp2 knockdown did not affect mitotic clonal expansion, but resulted in a marked decrease in superoxide production that is known to affect adipogenesis. These results suggest that Stamp1 and Stamp2 play critical roles in adipogenesis, but through different mechanisms.

المؤلفون: ten Freyhaus H; Department of Genetics, Harvard School of Public Health, Boston, MA 02115, USA., Calay ES, Yalcin A, Vallerie SN, Yang L, Calay ZZ, Saatcioglu F, Hotamisligil GS

المصدر: Cell metabolism [Cell Metab] 2012 Jul 03; Vol. 16 (1), pp. 81-9. Date of Electronic Publication: 2012 Jun 14.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101233170 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-7420 (Electronic) Linking ISSN: 15504131 NLM ISO Abbreviation: Cell Metab Subsets: MEDLINE

مواضيع طبية MeSH: Homeostasis*, Atherosclerosis/*metabolism , Inflammation Mediators/*metabolism , Macrophages/*metabolism , Membrane Proteins/*metabolism , NADP/*metabolism, Aged ; Amino Acid Sequence ; Animals ; Aorta/pathology ; Apolipoproteins E/deficiency ; Apolipoproteins E/genetics ; Atherosclerosis/pathology ; Bone Marrow Transplantation ; Cells, Cultured ; Female ; Humans ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-6/metabolism ; Lipopolysaccharides/pharmacology ; Macrophages/immunology ; Macrophages/pathology ; Male ; Membrane Proteins/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Nitric Oxide Synthase Type II/metabolism

مستخلص: The six-transmembrane protein Stamp2 plays an important role in metabolically triggered inflammation and insulin action. We report that Stamp2 is expressed in human and mouse macrophages, is regulated upon differentiation or activation, acts as an anti-inflammatory protein, and regulates foam cell formation. Absence of Stamp2 results in significant increases in cellular NADPH levels, and both NADPH homeostasis and the exaggerated inflammatory response of Stamp2(-/-) macrophages are rescued by exogenous wild-type but not by a reductase-deficient Stamp2 molecule. Chemical and genetic suppression of NADPH production in Stamp2(-/-) macrophages reverts the heightened inflammatory response. Stamp2 is detected in mouse and human atherosclerotic plaques, and its deficiency promotes atherosclerosis in mice. Furthermore, bone marrow transplantation experiments demonstrated that Stamp2 in myeloid cells is sufficient to protect against atherosclerosis. Our data reveal a role of Stamp2 in controlling intermediary metabolites to regulate inflammatory responses in macrophages and in progression of atherosclerosis.
(Copyright © 2012 Elsevier Inc. All rights reserved.)

المؤلفون: Wang L; Department of Molecular Biosciences and Center for Cancer Biomedicine, University of Oslo, Oslo, Norway., Jin Y, Arnoldussen YJ, Jonson I, Qu S, Maelandsmo GM, Kristian A, Risberg B, Waehre H, Danielsen HE, Saatcioglu F

المصدر: Cancer research [Cancer Res] 2010 Jul 15; Vol. 70 (14), pp. 5818-28. Date of Electronic Publication: 2010 Jun 29.

نوع المنشور: Journal Article

بيانات الدورية: Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 2984705R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-7445 (Electronic) Linking ISSN: 00085472 NLM ISO Abbreviation: Cancer Res Subsets: MEDLINE

مواضيع طبية MeSH: Membrane Proteins/*physiology , Neoplasm Proteins/*physiology , Oxidoreductases/*physiology , Prostatic Neoplasms/*pathology, Amino Acid Sequence ; Animals ; Apoptosis/genetics ; COS Cells ; Cell Cycle/genetics ; Cell Growth Processes/physiology ; Cell Line, Tumor ; Chlorocebus aethiops ; Chromones/pharmacology ; Down-Regulation ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Humans ; Male ; Membrane Proteins/biosynthesis ; Membrane Proteins/genetics ; Mice ; Mice, Nude ; Molecular Sequence Data ; Morpholines/pharmacology ; Neoplasm Proteins/biosynthesis ; Neoplasm Proteins/genetics ; Oxidoreductases/biosynthesis ; Oxidoreductases/genetics ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/metabolism ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; TNF-Related Apoptosis-Inducing Ligand/pharmacology

مستخلص: STAMP1 is predicted to encode a six-transmembrane protein whose expression is highly prostate enriched and is deregulated in prostate cancer. However, the biological role of STAMP1 in prostate cancer cells, or its expression profile at the protein level, is unknown. Here, we find that ectopic expression of STAMP1 significantly increased proliferation of DU145 prostate cancer cells as well as COS-7 cells in vitro; conversely, small interfering RNA-mediated knockdown of STAMP1 expression in LNCaP cells inhibited cell growth and, at least partially, induced cell cycle arrest. In parallel, there were alterations in cell cycle-regulatory gene expression. Knockdown of STAMP1 expression in LNCaP cells also induced significant apoptosis under basal conditions as well as in response to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) alone, or TRAIL + AKT inhibitor LY294002, previously established apoptotic agents in LNCaP cells. Consistently, LNCaP cells with short hairpin RNA-mediated knockdown of STAMP1 were dramatically retarded in their ability to grow as xenografts in nude mice. Interestingly, activation of extracellular signal-regulated kinase, which has previously been implicated in prostate cancer progression, was significantly increased on ectopic expression of STAMP1 in DU145 cells and, conversely, was strongly downregulated on STAMP1 knockdown in LNCaP cells. In the normal prostate, STAMP1 protein is localized to the cytosol and the cell membrane of the prostate epithelial cells; furthermore, its expression is increased in prostate cancer compared with normal prostate. Taken together, these data suggest that STAMP1 is required for prostate cancer growth, which may be a useful target in prostate cancer treatment.
((c)2010 AACR.)

المؤلفون: Lindstad T; Department of Molecular Biosciences, University of Oslo, Oslo, Norway., Jin Y, Wang L, Qu S, Saatcioglu F

المصدر: Nutrition and cancer [Nutr Cancer] 2010; Vol. 62 (7), pp. 891-5.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't; Review

بيانات الدورية: Publisher: Routledge Country of Publication: United States NLM ID: 7905040 Publication Model: Print Cited Medium: Internet ISSN: 1532-7914 (Electronic) Linking ISSN: 01635581 NLM ISO Abbreviation: Nutr Cancer Subsets: MEDLINE

مواضيع طبية MeSH: Membrane Proteins/*physiology , Neoplasm Proteins/*physiology , Oxidoreductases/*physiology , Prostatic Neoplasms/*etiology, Animals ; Antigens, Neoplasm/genetics ; Antigens, Neoplasm/physiology ; Humans ; Male ; Membrane Proteins/genetics ; Mice ; Neoplasm Proteins/genetics ; Nutritional Physiological Phenomena ; Oxidoreductases/genetics

مستخلص: Prostate cancer is the most diagnosed noncutaneous cancer among men in Western developed countries. Nutrition and environmental factors play a major role in the onset of the disease, but the molecular details for the contribution of each factor is elusive. In an effort to better understand the basic biology of prostate cancer, we identified a new protein family that is named the 6 trans-membrane protein of prostate (STAMP) that appear to have important functions in prostate cancer. At least one member of the STAMP family is also implicated in metabolic homeostasis and nutrition response. Here, we review the current biology of the STAMP proteins and how they may be implicated in disease states including cancer and metabolic syndrome.

المؤلفون: Wellen KE; Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA., Fucho R, Gregor MF, Furuhashi M, Morgan C, Lindstad T, Vaillancourt E, Gorgun CZ, Saatcioglu F, Hotamisligil GS

المصدر: Cell [Cell] 2007 May 04; Vol. 129 (3), pp. 537-48.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 0413066 Publication Model: Print Cited Medium: Print ISSN: 0092-8674 (Print) Linking ISSN: 00928674 NLM ISO Abbreviation: Cell Subsets: MEDLINE

مواضيع طبية MeSH: Food* , Metabolic Networks and Pathways*, Adipocytes/*metabolism , Inflammation/*metabolism , Membrane Proteins/*metabolism, 3T3-L1 Cells ; Adipose Tissue/metabolism ; Animals ; Cells, Cultured ; Female ; Glucose/metabolism ; Homeostasis ; Insulin/metabolism ; Insulin Resistance ; Lipid Metabolism ; Liver/metabolism ; Male ; Membrane Proteins/genetics ; Metabolic Syndrome/metabolism ; Mice ; Mice, Inbred C57BL ; Mutation

مستخلص: Metabolic and inflammatory pathways crosstalk at many levels, and, while required for homeostasis, interaction between these pathways can also lead to metabolic dysregulation under conditions of chronic stress. Thus, we hypothesized that mechanisms might exist to prevent overt inflammatory responses during physiological fluctuations in nutrients or under nutrient-rich conditions, and we identified the six-transmembrane protein STAMP2 as a critical modulator of this integrated response system of inflammation and metabolism in adipocytes. Lack of STAMP2 in adipocytes results in aberrant inflammatory responses to both nutrients and acute inflammatory stimuli. Similarly, in whole animals, visceral adipose tissue of STAMP2(-/-) mice exhibits overt inflammation, and these mice develop spontaneous metabolic disease on a regular diet, manifesting insulin resistance, glucose intolerance, mild hyperglycemia, dyslipidemia, and fatty liver disease. We conclude that STAMP2 participates in integrating inflammatory and metabolic responses and thus plays a key role in systemic metabolic homeostasis.

المؤلفون: Korkmaz CG; Department of Molecular Biosciences, University of Oslo, Postboks 1050 Blindern, 0316 Oslo, Norway., Korkmaz KS, Kurys P, Elbi C, Wang L, Klokk TI, Hammarstrom C, Troen G, Svindland A, Hager GL, Saatcioglu F

المصدر: Oncogene [Oncogene] 2005 Jul 21; Vol. 24 (31), pp. 4934-45.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE

مواضيع طبية MeSH: Membrane Proteins/*genetics , Neoplasm Proteins/*genetics , Prostatic Neoplasms/*genetics, Adenocarcinoma/genetics ; Amino Acid Sequence ; Cell Division ; Cell Line, Tumor ; Cloning, Molecular ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Molecular Sequence Data ; Organ Specificity ; Oxidoreductases ; Plasmids/genetics ; Sequence Alignment ; Sequence Homology, Amino Acid

مستخلص: We have identified a novel gene, six transmembrane protein of prostate 2 (STAMP2), named for its high sequence similarity to the recently identified STAMP1 gene. STAMP2 displays a tissue-restricted expression with highest expression levels in placenta, lung, heart, and prostate and is predicted to code for a 459-amino acid six transmembrane protein. Using a form of STAMP2 labeled with green flourescent protein (GFP) in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP2 is primarily localized to the Golgi complex, trans-Golgi network, and the plasma membrane. STAMP2 also localizes to vesicular-tubular structures in the cytosol and colocalizes with the Early Endosome Antigen1 (EEA1) suggesting that it may be involved in the secretory/endocytic pathways. STAMP2 expression is exquisitely androgen regulated in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Analysis of STAMP2 expression in matched normal and tumor samples microdissected from prostate cancer specimens indicates that STAMP2 is overexpressed in prostate cancer cells compared with normal prostate epithelial cells. Furthermore, ectopic expression of STAMP2 in prostate cancer cells significantly increases cell growth and colony formation suggesting that STAMP2 may have a role in cell proliferation. Taken together, these data suggest that STAMP2 may contribute to the normal biology of the prostate cell, as well as prostate cancer progression.

المؤلفون: Korkmaz KS; Department of Biology and the Biotechnology Centre of Oslo, University of Oslo, Postboks 1050 Blindern, 0316 Oslo, Norway., Elbi C, Korkmaz CG, Loda M, Hager GL, Saatcioglu F

المصدر: The Journal of biological chemistry [J Biol Chem] 2002 Sep 27; Vol. 277 (39), pp. 36689-96. Date of Electronic Publication: 2002 Jul 02.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Print ISSN: 0021-9258 (Print) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE

مواضيع طبية MeSH: Cell Membrane/*metabolism , Membrane Proteins/*biosynthesis , Membrane Proteins/*genetics , Prostatic Neoplasms/*metabolism, Amino Acid Sequence ; Animals ; Blotting, Northern ; COS Cells ; Cloning, Molecular ; DNA, Complementary/metabolism ; Databases as Topic ; Disease Progression ; Endosomes/metabolism ; Fluorescent Antibody Technique, Indirect ; Gene Expression Regulation, Neoplastic ; Humans ; In Situ Hybridization ; Male ; Membrane Proteins/chemistry ; Microscopy, Confocal ; Microscopy, Fluorescence ; Molecular Sequence Data ; Neoplasm Proteins ; Neoplasm Transplantation ; Oxidoreductases ; Plasmids/metabolism ; Protein Structure, Tertiary ; Sequence Homology, Amino Acid ; Time Factors ; Tumor Cells, Cultured

مستخلص: We have identified a novel gene, six transmembrane protein of prostate 1 (STAMP1), which is largely specific to prostate for expression and is predicted to code for a 490-amino acid six transmembrane protein. Using a form of STAMP1 labeled with green fluorescent protein in quantitative time-lapse and immunofluorescence confocal microscopy, we show that STAMP1 is localized to the Golgi complex, predominantly to the trans-Golgi network, and to the plasma membrane. STAMP1 also localizes to vesicular tubular structures in the cytosol and colocalizes with the early endosome antigen 1 (EEA1), suggesting that it may be involved in the secretory/endocytic pathways. STAMP1 is highly expressed in the androgen-sensitive, androgen receptor-positive prostate cancer cell line LNCaP, but not in androgen receptor-negative prostate cancer cell lines PC-3 and DU145. Furthermore, STAMP1 expression is significantly lower in the androgen-dependent human prostate xenograft CWR22 compared with the relapsed derivative CWR22R, suggesting that its expression may be deregulated during prostate cancer progression. Consistent with this notion, in situ analysis of human prostate cancer specimens indicated that STAMP1 is expressed exclusively in the epithelial cells of the prostate and its expression is significantly increased in prostate tumors compared with normal glands. Taken together, these data suggest that STAMP1 may have an important role in the normal prostate cell as well as in prostate cancer progression.