Download Gene Section S100A13 (S100 calcium binding protein A13) in Oncology and Haematology

Atlas of Genetics and Cytogenetics
in Oncology and Haematology
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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 Ca2+-binding EF-hands motifs and a
positively charged C-terminal region mediating the
interaction with specific target molecules.
Identity
Hugo: S100A13
Location: 1q21.3
Local order: Co-localized in a gene cluster with other
S100 genes on 1q21.3.
Expression
Highly expressed in skeletal muscle, heart, kidney,
pancreas, ovary, spleen and small intestine, follicle
cells of thyroid; moderate expression in prostate, testis,
colon and brain; little expression in thymus, lung, liver
and placenta, non detectable expression in leukocytes.
DNA/RNA
Description
The gene contains five exons and four introns; it is
composed of a variable 5' untranslated region, a 296 bp
coding sequence, a 3' untranslated region and a polyA
tail.
Localisation
Transcription
It may function in exocytosis, since it is one of the
targets of some antiallergic drugs, such as amlexanox
and cromolyn, which inhibit degranulation of mast
cells; marker of active angiogenesis in some tumours
and endometriosis; released with signal peptide-less
proteins such as FGF1 and IL-1alpha upon intracellular
stress conditions.
Cytosolic
Function
The gene has 5 alternatively spliced variants encoding
the same protein; the variant 1 represents the longest
transcript (951 bp), all the other variants have distinct
and shorter 5'UTR as compared to variant 1.
Protein
Homology
Description
68% homology with human S100A14 and 50.5% with
human S100A5 ; 86,7% with mouse S100A13.
Small homodimeric protein (98 amino-acids, M.W.
Schematic representation of the domains structure of S100A13 monomer.
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6)
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S100A13 (S100 calcium binding protein A13)
Barone C, et al.
heterogeneous aggregate of at least 3 distinct
histologies including epidermoid or squamous
carcinoma, adenocarcinoma and large cell carcinoma
with the potential for cure with surgical resection when
localized. Small cell lung carcinoma has a greater
tendency to be disseminated by the time of diagnosis
but is much more responsive to chemotherapy and
radiation compared to non-small cell lung cancer.
Prognosis
Poor; small cell carcinoma has the most aggressive
clinical course with median survival of only 2-4 months
without treatment.
Cytogenetics
Loss of heterozigosity in chromosome regions 3p
(fragile histidine triad, FHIT, locus), 12p, 13q (Rb1
locus) and 17p (p53 locus).
Oncogenesis
Inactivation of p16 by promoter hypermethylation is
more frequent in squamous cell carcinoma compared
with adenocarcinoma and is almost never found in
small-cell lung cancer; K-ras mutations are documented
only in non- small cell lung tumours particularly
adenocarcinoma. Overexpression of myc family
members and inactivation of p53, pRb and FHIT are
found in all histologic types of lung cancer. S100P and
S100A2 may be predictors of distant metastasis and
poor survival in non-small cell lung tumours since they
are overexpressed in tumours that metastatized during
the course of the disease; S100A13 expression
correlates with a more invasive phenotype in vitro.
Implicated in
Astrocytic gliomas
Disease
Astrocytic gliomas are the most common primary brain
tumours; they include WHO grade IV tumours, such as
glioblastomas with its variants and WHO grade III
tumours
(anaplastic
forms
of
astrocytoma,
oligodendroglioma and oligoastrocytoma ).
Prognosis
Poor for glioblastoma, relatively better for who grade
III tumours.
Cytogenetics
Anaplastic astrocytomas carry gain of chromosome 7
or 7q and deletions on chromosomes 6, 9p, 11p, 19q
and 22q. Glioblastomas demonstrate deletions of
chromosome 10 and allelic losses on 19q and 13q.
Oncogenesis
Homozigous deletion of CDKN2A, CDKN2B and
p14ARF(9p) (9p), negative regulators of cell cycle or
amplification of the cyclin-dependent kinase CDK4 are
frequent in astrocytoma gr. III and glioblastoma.
Glioblastoma and a subset of anaplastic astrocytoma
with no abnormality of CDK4 and CDKN2A carries
mutation in the retinoblastoma gene (Rb1); p53 pathway is frequently altered and PTEN is mutated in
30-40% of glioblastoma and in astrocytoma with poor
prognosis. Astrocytic gliomas generally stain positive
for S-100 proteins; S100-A13 is up-regulated in highgrade gliomas and correlated with microvessel density
and tumour grading.
References
Endometriosis
Wicki R, Schäfer BW, Erne P, Heizmann CW. Characterization
of the human and mouse cDNAs coding for S100A13, a new
member of the S100 protein family. Biochem Biophys Res
Commun 1996;227(2):594-599.
Disease
Endometriosis is characterized by the presence and
proliferation of functional endometrial glands and
stroma outside the uterine cavity. It is a multifactorial
genetic disorders. Increasing evidence points to the role
of angiogenesis in the disease pathogenesis and many
angiogenic factors and cytokines such as VEGF-A,
FGF1, endoglin and interleukin-1 alpha are upregulated in endometriotic lesions. S100A13 is overexpressed in endometriotic specimens, particularly in
microvascular endothelia.
Prognosis
It is a chronic and recurrent disease associated with
infertility.
Shishibori T, Oyama Y, Matsushita O, Yamashita K, Furuichi
H, Okabe A, Maeta H, Hata Y, Kobayashi R. Three distinct
anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to
S100A12 and S100A13 of the S100 protein family. Biochem J
1999;338 ( Pt 3):583-589.
Kersting M, Friedl C, Kraus A, Behn M, Pankow W,
Schuermann M. Differential frequencies of p16(INK4a)
promoter hypermethylation, p53 mutation, and K-ras mutation
in exfoliative material mark the development of lung cancer in
symptomatic chronic smokers. J Clin Oncol 2000;18(18):32213229.
Ridinger K, Schäfer BW, Durussel I, Cox JA, Heizmann CW.
S100A13. Biochemical characterization and subcellular
localization in different cell lines. J Biol Chem
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 histologyspecific methylation of CpG islands by exposure to tobacco
smoke in non-small cell lung cancer. Cancer Res
2001;61(8):3419-3424.
Disease
Lung cancer is the most preventable of all the major
forms of cancer since at least 75% of all cases
worldwide are due to tobacco smoking. It can be
classified into two main groups: small cell lung cancer
and non-small cell lung cancer. The latter group is a
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6)
Landriscina M, Bagalá C, Mandinova A, Soldi R, Micucci I,
Bellum S, Prudovsky I, Maciag T. Copper induces the
assembly of a multiprotein aggregate implicated in the release
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S100A13 (S100 calcium binding protein A13)
Barone C, et al.
of fibroblast growth factor 1 in response to stress. J Biol Chem
2001;276(27):25549-25557.
Hudelist G, Lass H, Keckstein J, Walter I, Wieser F, Wenzl R,
Mueller R, Czerwenka K, Kubista E, Singer CF. Interleukin
1alpha and tissue-lytic matrix metalloproteinase-1 are elevated
in ectopic endometrium of patients with endometriosis. Hum
Reprod 2005;20(6):1695-1701.
Landriscina M, Soldi R, Bagalá C, Micucci I, Bellum S,
Tarantini F, Prudovsky I, Maciag T. S100A13 participates in
the release of fibroblast growth factor 1 in response to heat
shock in vitro. J Biol Chem 2001;276(25):22544-22552.
Landriscina M, Schinzari G, Di Leonardo G, Quirino M,
Cassano A, D'Argento E, Lauriola L, Scerrati M, Prudovsky I,
Barone C. S100A13, a new marker of angiogenesis in human
astrocytic gliomas. J Neurooncol 2006;80(3):251-259.
Wistuba II, Gazdar AF, Minna JD. Molecular genetics of small
cell lung carcinoma. Semin Oncol 2001;28(2 Suppl 4):3-13.
(Review).
Li M, Zhang PF, Pan XW, Chang WR. Crystal structure study
on human S100A13 at 2.0 A resolution. Biochem Biophys Res
Commun 2007;356(3):616-621.
Mandinova A, Soldi R, Graziani I, Bagala C, Bellum S,
Landriscina M, Tarantini F, Prudovsky I, Maciag T. S100A13
mediates the copper-dependent stress-induced release of IL1alpha from both human U937 and murine NIH 3T3 cells. J
Cell Sci 2003;116(Pt 13):2687-2696.
Pierce A, Barron N, Linehan R, Ryan E, O'Driscoll L, Daly C,
Clynes M. Identification of a novel, functional role for S100A13
in invasive lung cancer cell lines. Eur J Cancer
2008;44(1):151-159.
Prudovsky I, Mandinova A, Soldi R, Bagala C, Graziani I,
Landriscina M, Tarantini F, Duarte M, Bellum S, Doherty H,
Maciag T. The non-classical export routes: FGF1 and IL1alpha point the way. J Cell Sci 2003;116(Pt 24):4871-4881.
(Review).
This article should be referenced as such:
Barone C, Bagalà C, Landriscina M. S100A13 (S100 calcium
binding protein A13). Atlas Genet Cytogenet Oncol
Haematol.2008;12(6):440-442.
Hayrabedyan S, Kyurkchiev S, Kehayov I. Endoglin (cd105)
and S100A13 as markers of active angiogenesis in
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)
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