MyMedR

Displaying publications 1 - 20 of 34 in total

Abstract:

Sort:

Abnormality in DNA-protein binding in ataxia-telangiectasia nuclear extracts

Mohamed R, Lavin MF

Biochem Biophys Res Commun, 1989 Feb 15;158(3):749-54.
PMID: 2537634

Anomalies in DNA replication, repair and recombination in ataxia-telangiectasia (A-T) point to a defect in structure or function of chromatin. In this study we have compared DNA-protein binding in nuclear extracts from control and A-T cells using two assay systems, filter-binding and DNA-accessibility. Interestingly, the extent of DNA protein binding over a range of protein concentration was significantly lower in A-T extracts. In addition the accessibility of the restriction enzyme Eco R1 to protein-bound plasmid was greater when A-T extracts were used. This is in keeping with the reduced binding observed in the filter-binding assay.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
The role of TGFbeta in human cancers

Wong SF, Lai LC

Pathology, 2001 Feb;33(1):85-92.
PMID: 11280615

Transforming growth factor beta (TGFbeta) is secreted as a large latent precursor from both normal and transformed cells which needs to be activated for biological activity. The active TGFbeta binds either directly to TbetaR-II or indirectly by binding to beta-glycan which then presents the TGFbeta to TbetaR-II. Formation of the TGFbeta-TbetaR-II complex rapidly leads to phosphorylation of TbetaR-I. TbetaR-I, in turn, phosphorylates receptor-specific Smads and induces their translocation into the nucleus. TGFbeta is able to act as a growth stimulator or inhibitor and elicits a broad spectrum of biological effects on various cell types. However, these cells may lose their sensitivity and responsiveness to TGFbeta. Down-regulation or loss of functional receptors, aberrant signal transduction pathways due to Smad mutations, loss of the cell's ability to activate latent TGFbeta, loss of the peptide itself or functional genes that control the transcription and translation of TGFbeta may contribute to development of cancer.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext The immunophenotypic patterns of follicle centre and mantle zone in Castleman's disease

Peh SC, Shaminie J, Poppema S, Kim LH

Singapore Med J, 2003 Apr;44(4):185-91.
PMID: 12952030

Castleman's disease is an uncommon disease and the histopathogenesis is poorly understood. This study aims to investigate their clinicopathological and immunophenotypic profile.

Matched MeSH terms: DNA-Binding Proteins/metabolism
The pattern and frequency of t(14;18) translocation and immunophenotype in Asian follicular lymphoma

Peh SC, Shaminie J, Tai YC, Tan J, Gan SS

Histopathology, 2004 Nov;45(5):501-10.
PMID: 15500654

Follicular lymphoma is frequently associated with t(14;18)(q32;q21) translocation. This study was undertaken to determine the pattern of Bcl-2, CD10 and Bcl-6 expression in relation to t(14;18) translocation in follicular lymphoma from a cohort of a multi-ethnic Asian population.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Host evasion by emerging paramyxoviruses: Hendra virus and Nipah virus v proteins inhibit interferon signaling

Rodriguez JJ, Horvath CM

Viral Immunol, 2004;17(2):210-9.
PMID: 15279700

Interferon (IFN) can activate Signal Transducer and Activator of Transcription (STAT) proteins to establish a cellular antiviral response and inhibit virus replication. Many viruses have evolved strategies to inhibit this antiviral mechanism, but paramyxoviruses are unique in their abilities to directly target the IFN-responsive STAT proteins. Hendra virus and Nipah virus (Henipaviruses) are recently emerged paramyxoviruses that are the causative agents of fatal disease outbreaks in Australia and peninsular Malaysia. Similar to other paramyxoviruses, Henipaviruses inhibit IFN signal transduction through a virus-encoded protein called V. Recent studies have shown that Henipavirus V proteins target STAT proteins by inducing the formation of cytoplasmically localized high molecular weight STAT-containing complexes. This sequestration of STAT1 and STAT2 prevents STAT activation and blocks antiviral IFN signaling. As the V proteins are important factors for host evasion, they represent logical targets for therapeutics directed against Henipavirus epidemics.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext Overexpression of WNT2 and TSG101 genes in colorectal carcinoma

Ma XR, Edmund Sim UH, Pauline B, Patricia L, Rahman J

Trop Biomed, 2008 Apr;25(1):46-57.
PMID: 18600204 MyJurnal

Colorectal carcinoma (CRC) arises as a result of mutational activation of oncogenes coupled with inactivation of tumour suppressor genes. Mutations in APC, K-ras and p53 have been commonly reported. In a previous study by our group, the tumour susceptibility gene 101 (TSG101) were found to be persistently upregulated in CRC cases. TSG101 was reported to be closely related to cancers of the breast, brain and colon, and its overexpression in human papillary thyroid carcinomas and ovarian carcinomas had previously been reported. The wingless-type MMTV integration site family member 2 (WNT2) is potentially important in the Wnt/beta-catenin pathway and upregulation of WNT2 is not uncommon in human cancers. In this study, we report the investigation for mutation(s) and expression pattern(s) of WNT2 and TSG101, in an effort to further understand their role(s) in CRC tumourigenesis. Our results revealed no mutation in these genes, despite their persistent upregulation in CRC cases studied.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Clinical relevance of CD10, BCL-6 and multiple myeloma-1 expression in diffuse large B-cell lymphomas in Malaysia

Peh SC, Gan GG, Lee LK, Eow GI

Pathol. Int., 2008 Sep;58(9):572-9.
PMID: 18801072 DOI: 10.1111/j.1440-1827.2008.02273.x

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and it is recognized to constitute a heterogenous group of neoplasms. It can be divided into germinal center B-cell-like (GCB) and non-GCB subgroups. The aim of the present study was to evaluate the utility of immunophenotype subgrouping of DLBCL in a cohort of multi-ethnic Asian patients. A total of 84 reconfirmed de novo DLBCL were immunostained for the expression of CD10, BCL-2, BCL-6 and multiple myeloma-1. Thirty-three (39.3%) had the GCB phenotype, and the remainder (60.7%), the non-GCB phenotype. The results concur with most reports using a similar method of stratification. Forty-five patients had complete demographic and phenotype studies and 42 patients did not have rituximab treatment and had sufficient data for survival rate analysis. Similar to other studies, patients with combined low and low-intermediate International Prognostic Index score had better overall survival (P = 0.006). But patients with GCB phenotype did not have better prognosis, and BCL-2 expression was not associated with better prognosis. The expression of BCL-6 was associated with lower overall survival rate (P = 0.038). No apparent difference in overall and disease-free survival was noted between patients with GCB and non-GCB disease. BCL-6 expression by tumor cells appears to be associated with poorer prognosis.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Purification and functional analysis of recombinant Acholeplasma laidlawii histone-like HU protein

Levitskiy SA, Sycheva AM, Kharlampieva DD, Oberto J, Kamashev DE, Serebryakova MV, et al.

Biochimie, 2011 Jul;93(7):1102-9.
PMID: 21443922 DOI: 10.1016/j.biochi.2011.03.005

HU is a most abundant DNA-binding protein in bacteria. This protein is conserved either in its heterodimeric form or in one of its homodimeric forms in all bacteria, in plant chloroplasts, and in some viruses. HU protein non-specifically binds and bends DNA as a hetero- or homodimer and can participate in DNA supercoiling and DNA condensation. It also takes part in some DNA functions such as replication, recombination, and repair. HU does not recognize any specific sequences but shows some specificity to cruciform DNA and to repair intermediates, e.g., nick, gap, bulge, 3'-overhang, etc. To understand the features of HU binding to DNA and repair intermediates, a fast and easy HU proteins purification procedure is required. Here we report overproduction and purification of the HU homodimers. The method of HU purification allows obtaining a pure recombinant non-tagged protein cloned in Escherichia coli. We applied this method for purification of Acholeplasma laidlawii HU and demonstrated that this protein possesses a DNA-binding activity and is free of contaminating nuclease activity. Besides that we have shown that expression of A. laidlawii ihf_hu gene in a slow-growing hupAB E. coli strain restores the wild-type growth indicating that aclHU can perform the basic functions of E. coli HU in vivo.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73

Wong SW, Tiong KH, Kong WY, Yue YC, Chua CH, Lim JY, et al.

Breast Cancer Res Treat, 2011 Jul;128(2):301-13.
PMID: 20686837 DOI: 10.1007/s10549-010-1055-0

Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Mismatch repair genes expression defects & association with clinicopathological characteristics in colorectal carcinoma

Kaur G, Masoud A, Raihan N, Radzi M, Khamizar W, Kam LS

Indian J Med Res, 2011 Aug;134:186-92.
PMID: 21911971

DNA mismatch repair gene (MMR) abnormalities are seen in 95 per cent of hereditary nonpolyposis colorectal cancer (HNPCC) and 10-15 per cent of sporadic colorectal cancers. There are no data on MMR abnormalities in Malaysian colorectal cancer patients. This study was aimed to determine the frequency of abnormal MMR gene protein expression in colorectal carcinoma in Northern Peninsular Malaysia using immunohistochemistry.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Isolation and characterization of two ABRE-binding proteins: EABF and EABF1 from the oil palm

Omidvar V, Abdullah SN, Ho CL, Mahmood M, Al-Shanfari AB

Mol Biol Rep, 2012 Sep;39(9):8907-18.
PMID: 22722992 DOI: 10.1007/s11033-012-1758-x

Abscisic acid (ABA) is an important phytohormone involved in the abiotic stress resistance in plants. The ABA-responsive element (ABRE) binding factors play significant roles in the plant development and response to abiotic stresses, but none so far have been isolated and characterized from the oil palm. Two ABA-responsive cDNA clones, named EABF and EABF1, were isolated from the oil palm fruits using yeast one-hybrid system. The EABF had a conserved AP2/EREBP DNA-binding domain (DNA-BD) and a potential nuclear localization sequence (NLS). No previously known DNA-BD was identified from the EABF1 sequence. The EABF and EABF1 proteins were classified as DREB/CBF and bZIP family members based on the multiple sequence alignment and phylogenetic analysis. Both proteins showed ABRE-binding and transcriptional activation properties in yeast. Furthermore, both proteins were able to trans-activate the down-stream expression of the LacZ reporter gene in yeast. An electrophoretic mobility shift assay revealed that in addition to the ABRE sequence, both proteins could bind to the DRE sequence as well. Transcriptional analysis revealed that the expression of EABF was induced in response to the ABA in the oil palm fruits and leaves, but not in roots, while the EABF1 was constitutively induced in all tissues. The expressions of both genes were strongly induced in fruits in response to the ABA, ethylene, methyl jasmonate, drought, cold and high-salinity treatments, indicating that the EABF and EABF1 might act as connectors among different stress signal transduction pathways. Our results indicate that the EABF and EABF1 are novel stress-responsive transcription factors, which are involved in the abiotic stress response and ABA signaling in the oil palm and could be used for production of stress-tolerant transgenic crops.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Fulltext Identification of a BET family bromodomain/casein kinase II/TAF-containing complex as a regulator of mitotic condensin function

Kim HS, Mukhopadhyay R, Rothbart SB, Silva AC, Vanoosthuyse V, Radovani E, et al.

Cell Rep, 2014 Mar 13;6(5):892-905.
PMID: 24565511 DOI: 10.1016/j.celrep.2014.01.029

Condensin is a central regulator of mitotic genome structure with mutants showing poorly condensed chromosomes and profound segregation defects. Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. We show that NCT and condensin bind similar genomic regions but only briefly colocalize during the periods of chromosome condensation and decondensation. This pattern of NCT binding at the core centromere, the region of maximal condensin enrichment, tracks the abundance of acetylated histone H4, as regulated by the Hat1-Mis16 acetyltransferase complex and recognized by the first Nrc1 bromodomain. Strikingly, mutants in NCT or Hat1-Mis16 restore the formation of segregation-competent chromosomes in cells containing defective condensin. These results are consistent with a model where NCT targets CKII to chromatin in a cell-cycle-directed manner in order to modulate the activity of condensin during chromosome condensation and decondensation.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Fulltext WDR5, ASH2L, and RBBP5 control the efficiency of FOS transcript processing

Teoh PL, Sharrocks AD

Cell Mol Biol Lett, 2014 Jun;19(2):215-32.
PMID: 24715476 DOI: 10.2478/s11658-014-0190-8

H3K4 trimethylation is strongly associated with active transcription. The deposition of this mark is catalyzed by SET-domain methyltransferases, which consist of a subcomplex containing WDR5, ASH2L, and RBBP5 (the WAR subcomplex); a catalytic SET-domain protein; and additional complexspecific subunits. The ERK MAPK pathway also plays an important role in gene regulation via phosphorylation of transcription factors, co-regulators, or histone modifier complexes. However, the potential interactions between these two pathways remain largely unexplored. We investigated their potential interplay in terms of the regulation of the immediate early gene (IEG) regulatory network. We found that depletion of components of the WAR subcomplex led to increased levels of unspliced transcripts of IEGs that did not necessarily reflect changes in their mature transcripts. This occurs in a manner independent from changes in the H3K4me3 levels at the promoter region. We focused on FOS and found that the depletion of WAR subcomplex components affected the efficiency of FOS transcript processing. Our findings show a new aspect of WAR subcomplex function in coordinating active transcription with efficient pre-mRNA processing.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Fulltext Combined protein- and nucleic acid-level effects of rs1143679 (R77H), a lupus-predisposing variant within ITGAM

Maiti AK, Kim-Howard X, Motghare P, Pradhan V, Chua KH, Sun C, et al.

Hum Mol Genet, 2014 Aug 1;23(15):4161-76.
PMID: 24608226 DOI: 10.1093/hmg/ddu106

Integrin alpha M (ITGAM; CD11b) is a component of the macrophage-1 antigen complex, which mediates leukocyte adhesion, migration and phagocytosis as part of the immune system. We previously identified a missense polymorphism, rs1143679 (R77H), strongly associated with systemic lupus erythematosus (SLE). However, the molecular mechanisms of this variant are incompletely understood. A meta-analysis of published and novel data on 28 439 individuals with European, African, Hispanic and Asian ancestries reinforces genetic association between rs1143679 and SLE [Pmeta = 3.60 × 10(-90), odds ratio (OR) = 1.76]. Since rs1143679 is in the most active region of chromatin regulation and transcription factor binding in ITGAM, we quantitated ITGAM RNA and surface protein levels in monocytes from patients with each rs1143679 genotype. We observed that transcript levels significantly decreased for the risk allele ('A') relative to the non-risk allele ('G'), in a dose-dependent fashion: ('AA' < 'AG' < 'GG'). CD11b protein levels in patients' monocytes were directly correlated with RNA levels. Strikingly, heterozygous individuals express much lower (average 10- to 15-fold reduction) amounts of the 'A' transcript than 'G' transcript. We found that the non-risk sequence surrounding rs1143679 exhibits transcriptional enhancer activity in vivo and binds to Ku70/80, NFKB1 and EBF1 in vitro, functions that are significantly reduced with the risk allele. Mutant CD11b protein shows significantly reduced binding to fibrinogen and vitronectin, relative to non-risk, both in purified protein and in cellular models. This two-pronged contribution (nucleic acid- and protein-level) of the rs1143679 risk allele to decreasing ITGAM activity provides insight into the molecular mechanisms of its potent association with SLE.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext The use of protein-DNA, chromatin immunoprecipitation, and transcriptome arrays to describe transcriptional circuits in the dehydrated male rat hypothalamus

Qiu J, Kleineidam A, Gouraud S, Yao ST, Greenwood M, Hoe SZ, et al.

Endocrinology, 2014 Nov;155(11):4380-90.
PMID: 25144923 DOI: 10.1210/en.2014-1448

The supraoptic nucleus (SON) of the hypothalamus is responsible for maintaining osmotic stability in mammals through its elaboration of the antidiuretic hormone arginine vasopressin. Upon dehydration, the SON undergoes a function-related plasticity, which includes remodeling of morphology, electrical properties, and biosynthetic activity. This process occurs alongside alterations in steady state transcript levels, which might be mediated by changes in the activity of transcription factors. In order to identify which transcription factors might be involved in changing patterns of gene expression, an Affymetrix protein-DNA array analysis was carried out. Nuclear extracts of SON from dehydrated and control male rats were analyzed for binding to the 345 consensus DNA transcription factor binding sequences of the array. Statistical analysis revealed significant changes in binding to 26 consensus elements, of which EMSA confirmed increased binding to signal transducer and activator of transcription (Stat) 1/Stat3, cellular Myelocytomatosis virus-like cellular proto-oncogene (c-Myc)-Myc-associated factor X (Max), and pre-B cell leukemia transcription factor 1 sequences after dehydration. Focusing on c-Myc and Max, we used quantitative PCR to confirm previous transcriptomic analysis that had suggested an increase in c-Myc, but not Max, mRNA levels in the SON after dehydration, and we demonstrated c-Myc- and Max-like immunoreactivities in SON arginine vasopressin-expressing cells. Finally, by comparing new data obtained from Roche-NimbleGen chromatin immunoprecipitation arrays with previously published transcriptomic data, we have identified putative c-Myc target genes whose expression changes in the SON after dehydration. These include known c-Myc targets, such as the Slc7a5 gene, which encodes the L-type amino acid transporter 1, ribosomal protein L24, histone deactylase 2, and the Rat sarcoma proto-oncogene (Ras)-related nuclear GTPase.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext Gelam honey attenuated radiation-induced cell death in human diploid fibroblasts by promoting cell cycle progression and inhibiting apoptosis

Tengku Ahmad TA, Jaafar F, Jubri Z, Abdul Rahim K, Rajab NF, Makpol S

BMC Complement Altern Med, 2014;14:108.
PMID: 24655584 DOI: 10.1186/1472-6882-14-108

The interaction between ionizing radiation and substances in cells will induce the production of free radicals. These free radicals inflict damage to important biomolecules such as chromosomes, proteins and lipids which consequently trigger the expression of genes which are involved in protecting the cells or repair the oxidative damages. Honey has been known for its antioxidant properties and was used in medical and cosmetic products. Currently, research on honey is ongoing and diversifying. The aim of this study was to elucidate the role of Gelam honey as a radioprotector in human diploid fibroblast (HDFs) which were exposed to gamma-rays by determining the expression of genes and proteins involved in cell cycle regulation and cell death.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext Sumoylation controls the timing of Tup1-mediated transcriptional deactivation

Ng CH, Akhter A, Yurko N, Burgener JM, Rosonina E, Manley JL

Nat Commun, 2015 Mar 13;6:6610.
PMID: 25766875 DOI: 10.1038/ncomms7610

The small ubiquitin-like modifier (SUMO) is implicated in various cellular activities, including transcriptional regulation. We previously showed that the yeast activator Gcn4 becomes sumoylated during activation, facilitating its eventual promoter eviction and transcriptional shut off. Here we show that the corepressor Tup1 is sumoylated, at two specific lysines, under various stress conditions. Mutation of these sites has no effect on Tup1 recruitment or RNAP II promoter occupancy immediately following induction. However, Tup1 levels subsequently decrease, while RNAP II and transcription increase in Tup1 mutant cells. Consistent with this, a Tup1 mutant displaying increased sumoylation led to reduced transcription. We also show that coordinated sumoylation of Gcn4 and Tup1 enhances Gcn4 promoter eviction and that multiple Tup1-interacting proteins become sumoylated after stress. Together, our studies provide evidence that coordinated sumoylation of Gcn4, Tup1 and likely other factors dampens activated transcription by stabilizing Tup1 binding and stimulating Gcn4 and RNAP II removal.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Fulltext The nucleoprotein of influenza A virus induces p53 signaling and apoptosis via attenuation of host ubiquitin ligase RNF43

Nailwal H, Sharma S, Mayank AK, Lal SK

Cell Death Dis, 2015 May 21;6:e1768.
PMID: 25996295 DOI: 10.1038/cddis.2015.131

The interplay between influenza virus and host factors to support the viral life cycle is well documented. Influenza A virus (IAV) proteins interact with an array of cellular proteins and hijack host pathways which are at the helm of cellular responses to facilitate virus invasion. The multifaceted nature of the ubiquitination pathway for protein regulation makes it a vulnerable target of many viruses including IAV. To this end we conducted a yeast two-hybrid screen to search for cellular ubiquitin ligases important for influenza virus replication. We identified host protein, RING finger protein 43 (RNF43), a RING-type E3 ubiquitin ligase, as a novel interactor of nucleoprotein (NP) of IAV and an essential partner to induce NP-driven p53-mediated apoptosis in IAV-infected cells. In this study, we demonstrate that IAV leads to attenuation of RNF43 transcripts and hence its respective protein levels in the cellular milieu whereas in RNF43 depleted cells, viral replication was escalated several folds. Moreover, RNF43 polyubiquitinates p53 which further leads to its destabilization resulting in a decrease in induction of the p53 apoptotic pathway, a hitherto unknown process targeted by NP for p53 stabilization and accumulation. Collectively, these results conclude that NP targets RNF43 to modulate p53 ubiquitination levels and hence causes p53 stabilization which is conducive to an enhanced apoptosis level in the host cells. In conclusion, our study unravels a novel strategy adopted by IAV for utilizing the much conserved ubiquitin proteasomal pathway.

Matched MeSH terms: DNA-Binding Proteins/metabolism*
Critical role of ARID3B in the expression of pro-apoptotic p53-target genes and apoptosis

Pratama E, Tian X, Lestari W, Iseki S, Ichwan SJ, Ikeda MA

Biochem Biophys Res Commun, 2015 Dec;468(1-2):248-54.
PMID: 26519881 DOI: 10.1016/j.bbrc.2015.10.121

ARID3A and ARID3B are transcriptional targets of p53. Recently, it has been reported that ARID3A plays a critical role in the transcriptional activation of pro-arrest p21 in response to DNA damage. However, the role of ARID3B in the p53 regulatory pathway remains poorly understood. Here we show that ARID3A and ARID3B specifically bind to putative ARID3-binding sites in p53 target genes in vitro and in vivo. ARID3B and, to a lesser extent, ARID3A silencing blocked transcriptional activation of pro-apoptotic p53 target genes, such as PUMA, PIG3, and p53. Furthermore, ectopic ARID3B, to a lesser extent, ARID3A expression activated the pro-apoptotic gene expression, and only ARID3B induced apoptosis. Finally, ARID3B but not ARID3A silencing blocked apoptosis induction following DNA damage. These results indicated that, although ARID3B and ARID3A share overlapping functions, ARID3B play a key role in the expression of pro-apoptotic p53-target genes and apoptosis.

Matched MeSH terms: DNA-Binding Proteins/metabolism
Analysis of Hereditary Nonpolyposis Colorectal Cancer in Malay Cohorts using Immunohistochemical Screening

Wan Juhari WK, Wan Abdul Rahman WF, Mohd Sidek AS, Abu Hassan MR, Ahmad Amin Noordin KB, Zakaria AD, et al.

Asian Pac J Cancer Prev, 2015;16(9):3767-71.
PMID: 25987035

BACKGROUND: Lynch syndrome (LS) is an inherited predisposition to colorectal, endometrial (uterine) and other cancers. Although most cancers are not inherited, about 5 percent (%) of people who have colorectal or endometrial cancer have the Lynch syndrome. It involves the alteration of mismatch repair (MMR) genes; MLH1, MSH2, MSH6 or PMS2. In this study, we analyzed the expression of MMR proteins in colorectal cancer in a Malay cohort by immunohistochemistry.
MATERIALS AND METHODS: A total of 17 patients were selected fulfilling one of the Bethesda criteria: colorectal cancer diagnosed in a patient aged less than 50 years old, having synchronous and metachronous colorectal cancer or with a strong family history. Immunohistochemical staining was performed on paraffin embedded tumour tissue samples using four antibodies: MLH1, MSH2, MSH6 and PMS2.
RESULTS: Twelve out of 17 patients (70.6%) were noted to have a family history. A total of 41% (n=7) of the patients had abnormal immunohistochemical staining with one or more of the four antibodies. Loss of expression were noted in 13 tumour tissues with a negative staining score <4. Of 13 tumour tissues, four showed loss expression of MLH1. For PMS2, loss of expression were noted in five cases. Both MSH2 and MSH6 showed loss of expression in two tumour tissues respectively.
CONCLUSIONS: Revised Bethesda criteria and immunohistochemical analysis constituted a convenient approach and is recommended to be a first-line screening for Lynch syndrome in Malay cohorts.

Matched MeSH terms: DNA-Binding Proteins/metabolism

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links