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Gene Section Mini Review Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Mini Review S100A13 (S100 calcium binding protein A13) Carlo Barone, Cinzia Bagalà, Matteo Landriscina Catholic University of Sacred Heart, Institute of Internal Medicine, Oncology Unit, Largo A. Gemelli 8, 00168 Roma, Itlaly Published in Atlas Database: February 2008 Online updated version: http://AtlasGeneticsOncology.org/Genes/S100A13ID44197ch1q21.html DOI: 10.4267/2042/38600 This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence. © 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology 11,47 kDa), with 2 Ca 2+ -binding EF-hands motifs and a Identity positively charged C-terminal region mediating the Hugo: S100A13 interaction with specific target molecules. Location: 1q21.3 Expression Local order: Co-localized in a gene cluster with other S100 genes on 1q21.3. Highly expressed in skeletal muscle, heart, kidney, pancreas, ovary, spleen and small intestine, follicle DNA/RNA cells of thyroid; moderate expression in prostate, testis, colon and brain; little expression in thymus, lung, liver Description and placenta, non detectable expression in leukocytes. The gene contains five exons and four introns; it is Localisation composed of a variable 5' untranslated region, a 296 bp Cytosolic coding sequence, a 3' untranslated region and a polyA tail. Function Transcription It may function in exocytosis, since it is one of the targets of some antiallergic drugs, such as amlexanox The gene has 5 alternatively spliced variants encoding and cromolyn, which inhibit degranulation of mast the same protein; the variant 1 represents the longest cells; marker of active angiogenesis in some tumours transcript (951 bp), all the other variants have distinct and endometriosis; released with signal peptide-less and shorter 5'UTR as compared to variant 1. proteins such as FGF1 and IL-1alpha upon intracellular Protein stress conditions. Homology Description 68% homology with human S100A14 and 50.5% with Small homodimeric protein (98 amino-acids, M.W. human S100A5 ; 86,7% with mouse S100A13. Schematic representation of the domains structure of S100A13 monomer. Atlas Genet Cytogenet Oncol Haematol. 2008;12(6) 440 S100A13 (S100 calcium binding protein A13) Barone C, et al. heterogeneous aggregate of at least 3 distinct Implicated in histologies including epidermoid or squamous Astrocytic gliomas carcinoma, adenocarcinoma and large cell carcinoma with the potential for cure with surgical resection when Disease localized. Small cell lung carcinoma has a greater Astrocytic gliomas are the most common primary brain tendency to be disseminated by the time of diagnosis tumours; they include WHO grade IV tumours, such as but is much more responsive to chemotherapy and glioblastomas with its variants and WHO grade III radiation compared to non-small cell lung cancer. tumours (anaplastic forms of astrocytoma, Prognosis oligodendroglioma and oligoastrocytoma ). Poor; small cell carcinoma has the most aggressive Prognosis clinical course with median survival of only 2-4 months Poor for glioblastoma, relatively better for who grade without treatment. III tumours. Cytogenetics Cytogenetics Loss of heterozigosity in chromosome regions 3p Anaplastic astrocytomas carry gain of chromosome 7 (fragile histidine triad, FHIT, locus), 12p, 13q (Rb1 or 7q and deletions on chromosomes 6, 9p, 11p, 19q locus) and 17p (p53 locus). and 22q. Glioblastomas demonstrate deletions of Oncogenesis chromosome 10 and allelic losses on 19q and 13q. Inactivation of p16 by promoter hypermethylation is Oncogenesis more frequent in squamous cell carcinoma compared Homozigous deletion of CDKN2A, CDKN2B and with adenocarcinoma and is almost never found in p14ARF(9p) (9p), negative regulators of cell cycle or small-cell lung cancer; K-ras mutations are documented amplification of the cyclin-dependent kinase CDK4 are only in non- small cell lung tumours particularly frequent in astrocytoma gr. III and glioblastoma. adenocarcinoma. Overexpression of myc family Glioblastoma and a subset of anaplastic astrocytoma members and inactivation of p53, pRb and FHIT are with no abnormality of CDK4 and CDKN2A carries found in all histologic types of lung cancer. S100P and mutation in the retinoblastoma gene (Rb1); p53 - S100A2 may be predictors of distant metastasis and pathway is frequently altered and PTEN is mutated in poor survival in non-small cell lung tumours since they 30-40% of glioblastoma and in astrocytoma with poor are overexpressed in tumours that metastatized during prognosis. Astrocytic gliomas generally stain positive the course of the disease; S100A13 expression for S-100 proteins; S100-A13 is up-regulated in high- correlates with a more invasive phenotype in vitro. grade gliomas and correlated with microvessel density and tumour grading. References Endometriosis Wicki R, Schäfer BW, Erne P, Heizmann CW. Characterization Disease of the human and mouse cDNAs coding for S100A13, a new member of the S100 protein family. Biochem Biophys Res Endometriosis is characterized by the presence and Commun 1996;227(2):594-599. proliferation of functional endometrial glands and Shishibori T, Oyama Y, Matsushita O, Yamashita K, Furuichi stroma outside the uterine cavity. It is a multifactorial H, Okabe A, Maeta H, Hata Y, Kobayashi R. Three distinct genetic disorders. Increasing evidence points to the role anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. Biochem J of angiogenesis in the disease pathogenesis and many 1999;338 ( Pt 3):583-589. angiogenic factors and cytokines such as VEGF-A, Kersting M, Friedl C, Kraus A, Behn M, Pankow W, FGF1, endoglin and interleukin-1 alpha are up- Schuermann M. Differential frequencies of p16(INK4a) regulated in endometriotic lesions. S100A13 is over- promoter hypermethylation, p53 mutation, and K-ras mutation expressed in endometriotic specimens, particularly in in exfoliative material mark the development of lung cancer in symptomatic chronic smokers. J Clin Oncol 2000;18(18):3221- microvascular endothelia. 3229. Prognosis Ridinger K, Schäfer BW, Durussel I, Cox JA, Heizmann CW. It is a chronic and recurrent disease associated with S100A13. Biochemical characterization and subcellular localization in different cell lines. J Biol Chem infertility. 2000;275(12):8686-8694. Lung cancer Kim DH, Nelson HH, Wiencke JK, Zheng S, Christiani DC, Wain JC, Mark EJ, Kelsey KT. p16(INK4a) and histology- Disease specific methylation of CpG islands by exposure to tobacco Lung cancer is the most preventable of all the major smoke in non-small cell lung cancer. Cancer Res forms of cancer since at least 75% of all cases 2001;61(8):3419-3424. worldwide are due to tobacco smoking. It can be Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I, Bellum S, Prudovsky I, Maciag T. Copper induces the classified into two main groups: small cell lung cancer assembly of a multiprotein aggregate implicated in the release and non-small cell lung cancer. The latter group is a Atlas Genet Cytogenet Oncol Haematol. 2008;12(6) 441 S100A13 (S100 calcium binding protein A13) Barone C, et al. of fibroblast growth factor 1 in response to stress. J Biol Chem Hudelist G, Lass H, Keckstein J, Walter I, Wieser F, Wenzl R, 2001;276(27):25549-25557. Mueller R, Czerwenka K, Kubista E, Singer CF. Interleukin Landriscina M, Soldi R, Bagalá C, Micucci I, Bellum S, 1alpha and tissue-lytic matrix metalloproteinase-1 are elevated Tarantini F, Prudovsky I, Maciag T. S100A13 participates in in ectopic endometrium of patients with endometriosis. Hum the release of fibroblast growth factor 1 in response to heat Reprod 2005;20(6):1695-1701. shock in vitro. J Biol Chem 2001;276(25):22544-22552. Landriscina M, Schinzari G, Di Leonardo G, Quirino M, Wistuba II, Gazdar AF, Minna JD. Molecular genetics of small Cassano A, D'Argento E, Lauriola L, Scerrati M, Prudovsky I, cell lung carcinoma. Semin Oncol 2001;28(2 Suppl 4):3-13. Barone C. S100A13, a new marker of angiogenesis in human (Review). astrocytic gliomas. J Neurooncol 2006;80(3):251-259. Mandinova A, Soldi R, Graziani I, Bagala C, Bellum S, Li M, Zhang PF, Pan XW, Chang WR. Crystal structure study Landriscina M, Tarantini F, Prudovsky I, Maciag T. S100A13 on human S100A13 at 2.0 A resolution. Biochem Biophys Res mediates the copper-dependent stress-induced release of IL- Commun 2007;356(3):616-621. 1alpha from both human U937 and murine NIH 3T3 cells. J Pierce A, Barron N, Linehan R, Ryan E, O'Driscoll L, Daly C, Cell Sci 2003;116(Pt 13):2687-2696. Clynes M. Identification of a novel, functional role for S100A13 Prudovsky I, Mandinova A, Soldi R, Bagala C, Graziani I, in invasive lung cancer cell lines. Eur J Cancer Landriscina M, Tarantini F, Duarte M, Bellum S, Doherty H, 2008;44(1):151-159. Maciag T. The non-classical export routes: FGF1 and IL- 1alpha point the way. J Cell Sci 2003;116(Pt 24):4871-4881. This article should be referenced as such: (Review). Barone C, Bagalà C, Landriscina M. S100A13 (S100 calcium binding protein A13). Atlas Genet Cytogenet Oncol Hayrabedyan S, Kyurkchiev S, Kehayov I. Endoglin (cd105) and S100A13 as markers of active angiogenesis in Haematol.2008;12(6):440-442. endometriosis. Reprod Biol 2005;5(1):51-67. Hayrabedyan S, Kyurkchiev S, Kehayov I. FGF-1 and S100A13 possibly contribute to angiogenesis in endometriosis. J Reprod Immunol 2005;67(1-2):87-101. (Review). Atlas Genet Cytogenet Oncol Haematol. 2008;12(6) 442 .
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