Deregulation of RAD21 and RUNX1 expression in endometrial cancer

Supernat,Anna; Łapińska-Szumczyk,Sylwia; Sawicki,Sambor; Wydra,Dariusz; Biernat,Wojciech; Żaczek,Anna J.

doi:10.3892/ol.2012.794

Deregulation of RAD21 and RUNX1 expression in endometrial cancer

Authors:
- Anna Supernat
- Sylwia Łapińska-Szumczyk
- Sambor Sawicki
- Dariusz Wydra
- Wojciech Biernat
- Anna J. Żaczek
View Affiliations

Affiliations: Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, 80-211 Gdańsk, Poland, Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdańsk, 80-402 Gdańsk, Poland, Department of Gynaecology, Gynaecological Oncology and Gynaecological Endocrinology, Medical University of Gdańsk, 80-402 Gdańsk, Poland, Department of Pathomorphology, Medical University of Gdańsk, 80-211 Gdańsk, Poland
Published online on: July 9, 2012 https://doi.org/10.3892/ol.2012.794
Pages: 727-732

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Cohesins and cohesin-regulated genes are deregulated in numerous types of human cancer. However, data concerning their status and role in endometrial cancer are scarce. This study aimed to determine the clinical significance of double-strand-break repair protein rad21 homolog (RAD21) and runt-related transcription factor 1 (RUNX1) gene dosage and mRNA expression in endometrial cancer. RAD21 is a component of the cohesin complex, crucial for chromosome segregation and DNA repair. RUNX1 is the transcription factor implicated in RAD21 regulation. The study group included 144 endometrial cancer patients. RAD21 and RUNX1 expression profiles were measured by reverse-transcription quantitative PCR. RAD21 gene dosage was determined by quantitative PCR. RAD21 gene dosage was associated with RAD21 mRNA expression (ρ=0.22; p=0.009). Furthermore, RAD21 expression strongly correlated with RUNX1 expression (ρ=0.43; p<0.0000001). Increased RAD21 gene dosage correlated with more advanced tumor stage (p=0.021), higher grade (p=0.021), cervical involvement (p=0.01) and the absence of obesity (p=0.025), while RAD21 mRNA expression correlatd with cervical involvement (p=0.027). The mRNA expression of RAD21 and RUNX1 was found to be deregulated and co-dependent in endometrial cancer. RAD21 gene dosage is associated with unfavorable tumor characteristics. However, elucidating the role of these molecular markers in endometrial oncogenesis requires further investigation, including functional studies and survival analysis.

View Figures

View References

1.	American Cancer SocietyCancer Facts & Figures 2011AtlantaAmerican Cancer Society2011
2.	C MichaelisR CioskK NasmythCohesins: chromosomal proteins that prevent premature separation of sister chromatidsCell913545199710.1016/S0092-8674(01)80007-69335333
3.	V GuacciD KoshlandA StrunnikovA direct link between sister chromatid cohesion and chromosome condensation revealed through the analysis of MCD1 in S. cerevisiaeCell914757199710.1016/S0092-8674(01)80008-89335334
4.	E WatrinJM PetersCohesin and DNA damage repairExp Cell Res31226872693200610.1016/j.yexcr.2006.06.02416876157
5.	E SonodaT MatsusakaC MorrisonScc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cellsDev Cell1759770200110.1016/S1534-5807(01)00088-011740938
6.	JA HorsfieldSH AnagnostouJK HuCohesin-dependent regulation of Runx genesDevelopment13426392649200710.1242/dev.00248517567667
7.	C BauschS NooneJM HenryTranscription alters chromosomal locations of cohesin in Saccharomyces cerevisiaeMol Cell Biol2785228532200710.1128/MCB.01007-0717923700
8.	JM AtienzaRB RothC RosetteSuppression of RAD21 gene expression decreases cell growth and enhances cytotoxicity of etoposide and bleomycin in human breast cancer cellsMol Cancer Ther4361368200515767545
9.	H XuM YanJ PatraEnhanced RAD21 cohesin expression confers poor prognosis and resistance to chemotherapy in high grade luminal, basal and HER2 breast cancersBreast Cancer Res13R9201110.1186/bcr281421255398
10.	K OikawaT OhbayashiT KiyonoExpression of a novel human gene, human wings apart-like (hWAPL), is associated with cervical carcinogenesis and tumor progressionCancer Res6435453549200410.1158/0008-5472.CAN-03-382215150110
11.	G YamamotoT IrieT AidaY NagoshiR TsuchiyaT TachikawaCorrelation of invasion and metastasis of cancer cells, and expression of the RAD21 gene in oral squamous cell carcinomaVirchows Arch448435441200610.1007/s00428-005-0132-y16416296
12.	KP PorkkaTL TammelaRL VessellaT VisakorpiRAD21 and KIAA0196 at 8q24 are amplified and overexpressed in prostate cancerGenes Chromosomes Cancer39110200410.1002/gcc.1028914603436
13.	B RyuDS KimAM DelucaRM AlaniComprehensive expression profiling of tumor cell lines identifies molecular signatures of melanoma progressionPLoS One2e594200710.1371/journal.pone.000059417611626
14.	J PlanagumàM Díaz-FuertesA Gil-MorenoA differential gene expression profile reveals overexpression of RUNX1/AML1 in invasive endometrioid carcinomaCancer Res6488468853200415604243
15.	H XuK BalakrishnanJ MalaterreRad21-cohesin haploinsufficiency impedes DNA repair and enhances gastrointestinal radiosensitivity in micePLoS One5e12112201010.1371/journal.pone.001211220711430
16.	H XuJM TomaszewskiMJ McKayCan corruption of chromosome cohesion create a conduit to cancer?Nat Rev Cancer11199210201110.1038/nrc301821326324
17.	K BlythER CameronJC NeilThe RUNX genes: gain or loss of function in cancerNat Rev Cancer5376387200510.1038/nrc160715864279
18.	DR RhodesJ YuK ShankerLarge-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progressionProc Natl Acad Sci USA10193099314200410.1073/pnas.040199410115184677
19.	LJ van ‘t VeerH DaiMJ van de VijverGene expression profiling predicts clinical outcome of breast cancerNature415530536200211823860
20.	OD RøeE AnderssenE HelgeGenome-wide profile of pleural mesothelioma versus parietal and visceral pleura: the emerging gene portrait of the mesothelioma phenotypePLoS One4e6554200919662092
21.	A DollM GonzalezM AbalAn orthotopic endometrial cancer mouse model demonstrates a role for RUNX1 in distant metastasisInt J Cancer125257263200910.1002/ijc.2433019384951
22.	PV SpirinF BaskaranNN OrlovaDownregulation of activated leukemic oncogenes AML1-ETO and RUNX1(K83N) expression with RNA-interferenceMol Biol (Mosk)448768882010(In Russian)
23.	K InoueY ItoNeuroblastoma cell proliferation is sensitive to changes in levels of RUNX1 and RUNX3 proteinGene487151155201110.1016/j.gene.2011.05.01621640801
24.	T NiiniJ KanervaK VettenrantaUM Saarinen-PihkalaS KnuutilaAML1 gene amplification: a novel finding in childhood acute lymphoblastic leukemiaHaematologica85362366200010756360
25.	KA JanesRUNX1 and its understudied role in breast cancerCell Cycle1034613465201110.4161/cc.10.20.1802922024923
26.	R BeroukhimCH MermelD PorterThe landscape of somatic copy-number alteration across human cancersNature463899905201010.1038/nature0882220164920
27.	S PecorelliRevised FIGO staging for carcinoma of the vulva, cervix, and endometriumInt J Gynaecol Obstet105103104200910.1016/j.ijgo.2009.02.01219367689
28.	AT BaronN MaihleNadir CA125 concentration as a prognostic indicator in ovarian cancerNat Clin Pract Oncol2288289200510.1038/ncponc017816264982
29.	WE ConsultationAppropriate body-mass index for Asian populations and its implications for policy and intervention strategiesLancet363157163200410.1016/S0140-6736(03)15268-314726171
30.	J VandesompeleK De PreterF PattynAccurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genesGenome Biol3RESEARCH0034200210.1186/gb-2002-3-7-research003412184808
31.	MW PfafflA new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Res29e45200110.1093/nar/29.9.e4511328886
32.	A ZaczekA MarkiewiczJ JaskiewiczClinical evaluation of developed PCR-based method with hydrolysis probes for TOP2A copy number evaluation in breast cancer samplesClin Biochem43891898201010.1016/j.clinbiochem.2010.04.06020441774
33.	S CovoJW WestmorelandDA GordeninMA ResnickCohesin is limiting for the suppression of DNA damage-induced recombination between homologous chromosomesPLoS Genet6e1001006201010.1371/journal.pgen.100100620617204
34.	PR PottsMH PorteusH YuHuman SMC5/6 complex promotes sister chromatid homologous recombination by recruiting the SMC1/3 cohesin complex to double-strand breaksEMBO J2533773388200610.1038/sj.emboj.760121816810316
35.	AV RulinaPV SpirinVS PrassolovActivated leukemic oncogenes AML1-ETO and c-kit: role in development of acute myeloid leukemia and current approaches for their inhibitionBiochemistry (Mosc)7516501666201010.1134/S000629791013009221417999
36.	VI GaidzikL BullingerRF SchlenkRUNX1 mutations in acute myeloid leukemia: results from a comprehensive genetic and clinical analysis from the AML study groupJ Clin Oncol2913641372201110.1200/JCO.2010.30.792621343560
37.	S RamaswamyKN RossES LanderTR GolubA molecular signature of metastasis in primary solid tumorsNat Genet334954200310.1038/ng106012469122
38.	M KadotaHH YangB GomezDelineating genetic alterations for tumor progression in the MCF10A series of breast cancer cell linesPLoS One5e9201201010.1371/journal.pone.000920120169162
39.	M AbalJ PlanagumaA Gil-MorenoMolecular pathology of endometrial carcinoma: transcriptional signature in endometrioid tumorsHistol Histopathol21197204200616329044
40.	J PlanagumàM AbalA Gil-MorenoUp-regulation of ERM/ETV5 correlates with the degree of myometrial infiltration in endometrioid endometrial carcinomaJ Pathol207422429200516175655
41.	J PlanagumàM GonzalezA DollThe up-regulation profiles of p21WAF1/CIP1 and RUNX1/AML1 correlate with myometrial infiltration in endometrioid endometrial carcinomaHum Pathol3710501057200616867868
42.	RP BirkenbihlS SubramaniCloning and characterization of rad21 an essential gene of Schizosaccharomyces pombe involved in DNA double-strand-break repairNucleic Acids Res2066056611199210.1093/nar/20.24.66051480481
43.	C SjögrenK NasmythSister chromatid cohesion is required for postreplicative double-strand break repair in Saccharomyces cerevisiaeCurr Biol11991995200111448778