SEARCH · PubMed Health

Results for “Protein Array Analysis”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 919 records · Page 51Linked to original sources

PubMed2004

Multiplex GPCR assay in reverse transfection cell microarrays.

G protein-coupled receptors (GPCRs) are a superfamily of proteins that include some of the most important drug targets in the pharmaceutical industry. Despite the success of this group of drugs, there remains a need to identify GPCR-targeted drugs with greater selectivity, to develop screening assays for validated targets, and to identify ligands for orphan receptors. To address these challenges, the authors have created a multiplexed GPCR assay that measures greater than 3000 receptor: ligand interactions in a single microplate. The multiplexed assay is generated by combining reverse transfection in a 96-well plate format with a calcium flux readout. This assay quantitatively measures receptor activation and inhibition and permits the determination of compound potency and selectivity for entire families of GPCRs in parallel. To expand the number of GPCR targets that may be screened in this system, receptors are cotransfected with plasmids encoding a promiscuous G protein, permitting the analysis of receptors that do not normally mobilize intracellular calcium upon activation. The authors demonstrate the utility of reverse transfection cell microarrays to GPCR-targeted drug discovery with examples of ligand selectivity screening against a panel of GPCRs as well as dose-dependent titrations of selected agonists and antagonists.

Dose-Response Relationship, Drug↗

PubMed2006

STAT3 is activated in a subset of the Ewing sarcoma family of tumours.

STAT3 is an oncogene that regulates critical cellular processes and whose constitutive activation has been demonstrated to correlate with biological and clinical features in many types of human malignancy. In this study, STAT3 activation was assessed in the Ewing sarcoma family of tumours (ESFT), which is characterized by fusion of the EWS gene with one of several Ets transcription factors, most commonly EWS-FLI1. STAT3 activation was assessed by immunohistochemistry using a monoclonal antibody specific for tyrosine(705)-phosphorylated STAT3 (pSTAT3(tyr705)) and a tissue microarray containing 49 paraffin-embedded ESFT tumours with known EWS translocations. Twenty-five (51%) tumours were pSTAT3(tyr705)-positive, as defined by more than 10% tumour cell immunostaining. STAT3 activation correlated with tumour site at presentation, with pSTAT3(tyr705)-negative ESFT involving axial sites predominantly (p = 0.008). Notably, among 31 patients who presented with localized disease, high-level STAT3 activation correlated with better overall survival (p = 0.02). STAT3 activation was not directly related to EWS-FLI1 expression, since EWS-FLI1 transfection did not result in STAT3 activation. Furthermore, detailed molecular analysis indicated that STAT3 activation may be seen with EWS-FLI1 or EWS-ERG and appears to be independent of EWS-FLI1 fusion type. In conclusion, STAT3 activation is present in approximately half of ESFT and correlates with clinical features. The role of STAT3 activation in ESFT pathogenesis seems to be independent of the type of EWS/Ets translocation.

Adolescent↗

PubMed2004

Target specificity analysis of the Abl kinase using peptide microarray data.

Protein kinases play an important role in cellular signalling. The reliable prediction of their substrates is of high importance for the deciphering of signalling pathways. A recently developed peptide microarray technology for the charcterisation of protein kinases delivers data on the individual phosphorylation status of each single member of a large peptide library. This data can be used to approximate the substrate specificity of the investigated kinase. We present an approach to process the collected information using a combination of a weight matrix approach and a nearest neighbor approach. Experiments with the protein-tyrosine kinase Abl are conducted to validate the results. Randomly selected peptides (1433) are used to estimate the substrate preferences of the kinase. The obtained prediction results are compared with standard methods. The new approach is tested further on bona fide Abl phosphorylation sites.

Binding Sites↗

PubMedDate not supplied

Tissue microarray analysis of FAS, Bcl-2, Bcl-x, ER, PgR, Hsp60, p53 and Her2-neu in breast carcinoma.

BACKGROUND: The aim of this study was to detect immunohistochemical markers in breast carcinoma by means of tissue microarray analysis (TMA) and to associate their expressions with clinicopathological features and prognosis. Fatty acid synthase, bcl-2, bcl-x, p53, estrogen and progesterone receptors, heat shock protein 60 and Her2-neu (c-erbB-2) were evaluated in a group of 149 breast carcinoma patients with a 5-year follow-up period. MATERIALS AND METHODS: TMA blocks were made by using duplicate 0.6-mm diameter tissue cores from each paraffin block. RESULTS: Statistical analysis revealed that tumor stage (p=0.003) and node status (p=0.001) were the only two prognostic markers of disease-free survival. Moreover, FAS and bcl-x showed an independent effect on recurrence (p=0.005). The node status was the only marker of overall survival (p=0.05). CONCLUSION: Our data confirmed recent reports associating the stage of disease, FAS and Bcl-x expressions with recurrence and outcome. These data demonstrated that TMA is an effective substitute for conventional histochemical-immunohistochemical techniques.

Breast Neoplasms↗

PubMed2005

Expression of bcl-3 in chronic lymphocytic leukemia correlates with trisomy 12 and abnormalities of chromosome 19.

The bcl-3 gene at chromosome 19q13 encodes a member of the IkB family involved in regulating the nuclear factor kB pathway. Originally identified by its involvement in the t(14:19)(q32;q13), bcl-3 expression recently has been reported in 12% of non-Hodgkin lymphomas and 41% of Hodgkin lymphomas. Because the t(14;19) is detected most commonly in chronic lymphocytic leukemia (CLL), we assessed for bcl-3 expression using immunohistochemical analysis in 72 CLL cases with immunophenotypic and cytogenetic data. Of 72 CLL cases, 12 (17%) were bcl-3+. Expression of bcl-3 correlated with an atypical immunophenotype, defined using the World Health Organization scoring system. Expression also correlated with trisomy 12 and chromosome 19 abnormalities but was not limited to cases with the t(14:19)(q32;q13). Although the mechanism of bcl-3 expression is unclear, these results raise the possibility that bcl-3 may be involved in the pathogenesis of this subset of tumors and could be a potential target for investigational therapies.

Adult↗

PubMed2004

Protein microarrays for multiplex analysis of signal transduction pathways.

We have developed a multiplexed reverse phase protein (RPP) microarray platform for simultaneous monitoring of site-specific phosphorylation of numerous signaling proteins using nanogram amounts of lysates derived from stimulated living cells. We first show the application of RPP microarrays to the study of signaling kinetics and pathway delineation in Jurkat T lymphocytes. RPP microarrays were used to profile the phosphorylation state of 62 signaling components in Jurkat T cells stimulated through their membrane CD3 and CD28 receptors, identifying a previously unrecognized link between CD3 crosslinking and dephosphorylation of Raf-1 at Ser259. Finally, the potential of this technology to analyze rare primary cell populations is shown in a study of differential STAT protein phosphorylation in interleukin (IL)-2-stimulated CD4(+)CD25(+) regulatory T cells. RPP microarrays, prepared using simple procedures and standard microarray equipment, represent a powerful new tool for the study of signal transduction in both health and disease.

CD3 Complex↗

PubMed2005

The microarray expression analysis identifies BAX as a mediator of beta-carotene effects on apoptosis.

Beta-carotene is a ubiquitous compound rich in foods. However, there are conflicting reports regarding its role in carcinogenesis. We performed a microarray expression analysis in normal [human umbilical vein endothelial cells (HUVECs)] and neoplastic (melanoma A375 and myelomonocytic leukemia U937) actively proliferating cells and found evidence that beta-carotene stimulated vital cellular functions in the former and suppressed them in the latter. These differential effects correlated with the expression of the proapoptotic BCL2-associated X protein (BAX), which was downregulated in HUVECs and upregulated in the two neoplastic cell lines. The quantitative expression analysis using real-time polymerase chain reaction largely confirmed the inhibition of B-cell CLL/lymphoma 2 (BCL2) pathway-mediated apoptosis in HUVECs and its activation in melanoma and leukemic cells. The assays for apoptosis, detecting DNA breaks and caspase activation, showed consistent proapoptotic and antiapoptotic effects in U937 and HUVEC lines, respectively. However, beta-carotene-induced expression changes of BAX and other BCL2 pathway genes did not lead to the predicted induction of apoptosis in the A375 cells.

Antioxidants↗

PubMed2004

Analysis of KIT (CD117) expression in gallbladder carcinomas by tissue microarray.

AIMS: KIT (CD117) is a transmembrane tyrosinase-kinase receptor which has been related to cell proliferation, differentiation, adhesion and control of apoptosis. If present, KIT may provide a suitable target for tumour therapy. In this study, we report the presence of KIT in primary and metastatic gallbladder carcinomas. METHODS: Formalin-fixed and paraffin-embedded specimens of 57 primary gallbladder carcinomas and 18 corresponding metastases were stained using a tissue microarray technique and two different antibodies. RESULTS: Only three tumours stained for KIT. With a polyclonal antibody only one well differentiated papillary adenocarcinoma was immunoreactive. With a monoclonal antibody two additional poorly differentiated tubular adenocarcinoma showed weak and focal immunostaining. CONCLUSIONS: KIT immunoreactivity is infrequent in gallbladder carcinoma. Thus, routine screening of tumour tissues for KIT by immunohistochemistry appears to be cost-ineffective and cannot be recommended. Moreover, the lack of substantial KIT immunoreactivity in both primary and metastatic gallbladder carcinoma tissues does not provide a rationale to investigate imatinib mesylate therapy in clinical trials including patients with advanced disease.

Adenocarcinoma↗

PubMed2003

Calretinin expression in human normal and neoplastic tissues: a tissue microarray analysis on 5233 tissue samples.

Calretinin is a calcium-binding protein expressed in different normal and neoplastic tissues. Early studies suggested that calretinin is a useful marker to differentiate adenocarcinomas from malignant mesotheliomas of the lung, but subsequent work has shown that calretinin can be expressed in several other tumor types. To systematically investigate the epidemiology of calretinin expression in normal and neoplastic tissues, we used tissue microarrays (TMAs) to analyze the immunohistochemically detectable expression of calretinin in 5233 tissue samples from 128 different tumor categories and 76 different normal tissue types. At least 1 case with weak expression could be found in 74 of 128 (58%) different tumor types and 46 entities (36%) had at least 1 tumor with strong positivity. In normal tissues, a particularly strong expression was found in Leydig cells of the testis, neurons of the brain, theca-lutein and theca interna cells of the ovary, and mesothelium. In tumors, strong calretinin expression was most frequently found in malignant mesotheliomas (6 of 7), Leydig cell tumors of the testis (5 of 5), adenomas of adrenal gland (5 of 9), and adenomatoid tumors (4 of 9). In summary, calretinin is frequently expressed in many different tumor types. Metastases of various different origins must be included in the differential diagnosis of calretinin-positive pleura tumors.

Biomarkers↗

PubMed2006

Expression of Wnt-signaling pathway proteins in intraductal papillary mucinous neoplasms of the pancreas: a tissue microarray analysis.

Abrogation of the Wnt-signaling pathway is implicated in the carcinogenesis of several malignancies, especially colorectal cancer where up to 90% of cases are thought to have impaired Wnt signaling. It is less frequently involved in conventional ductal pancreatic adenocarcinoma. This pathway has not been explored in intraductal papillary mucinous neoplasms (IPMNs) of the pancreas previously and formed the basis of this study. A tissue microarray of 18 cases of IPMN was stained for proteins involved in the Wnt pathway: adenomatous polyposis coli (APC), pan-beta-catenin, axin 2, glycogen synthase 3alphabeta and 3beta, c-myc, E-cadherin, and cyclin D1. The IPMNs were classified as 8 adenomas, 3 borderline, and 7 cases with carcinoma in situ and/or invasive carcinoma, occurring in 13 females, and the overall age range was 45 to 73 years. Immunohistochemical analysis showed nuclear beta-catenin staining in 7 (39%) of the 18 cases. The cases with nuclear beta-catenin localization included 1 adenoma, 2 borderline IPMN, and 4 carcinomas in situ and/or invasive carcinomas. Seven cases showed absence of APC immunostaining and these included 4 cases with nuclear beta-catenin localization. Fourteen cases displayed marked diffuse up-regulation of c-myc protein, and 12 cases also showed diffuse cyclin D1 protein overexpression. E-cadherin expression was intense and membrane in location (comparable to normal tissue) in 6 of 8 adenomas (no tissue was available in 1 case). Decreased E-cadherin staining was noted in 8 cases where tissue was available for assessment. There was progressive decrease in membrane staining of E-cadherin in 2 of 3 borderline lesions, 1 of 2 carcinomas in situ, and 4 of 5 invasive carcinomas. All other immunostains were either normal in distribution or did not show any correlation with beta-catenin or clinicopathologic parameters. In conclusion, 7 (39%) of 18 cases of IPMN in this study demonstrated abnormal localization of beta-catenin, 4 of which also lacked APC expression. Of 5 carcinomas arising in IPMN, 4 displayed a decrease in E-cadherin expression. There was also a trend for the higher grades of IPMN to show nuclear localization of beta-catenin. These findings suggest that a proportion of cases of IPMN may show abnormalities in the Wnt-signaling pathway with consequent altered expression of downstream related proteins.

Adenoma↗

PubMed2006

Friend leukaemia integration-1 expression in malignant and benign tumours: a multiple tumour tissue microarray analysis using polyclonal antibody.

BACKGROUND: Friend leukaemia integration-1 (FLI-1) antibody is a useful marker for Ewing's sarcoma/primitive neuroectodermal tumour (EWS/PNET) and vascular tumours. However, it is also expressed in subsets of lymphoblastic lymphoma, Merkel cell carcinoma (MCC) and desmoplastic small round cell tumour (DSRCT). AIM: To determine expression of FLI-1 in various benign and malignant neoplasms, by immunohistochemical analysis on 4323 tumours using multiple tumour microarrays, as well as on whole sections. RESULTS: FLI-1 was expressed in 46/62 EWS/PNETs, 2/3 olfactory neuroblastomas, 7/102 small cell carcinomas of the lung, 10/34 MCCs, 1/14 rhabdomyosarcoma, 19/132 non-Hodgkin's lymphomas, 2/3 DSRCTs, and in 53/74 benign and malignant vascular tumours. In addition, 27/508 squamous cell carcinomas, 19/837 adenocarcinomas, 10/400 urothelial bladder cancers, 1/40 basal cell carcinomas, 3/29 liposarcomas, 1/40 glioblastoma multiforme and 9/29 medullar carcinomas of the breast expressed FLI-1. The sensitivity and specificity of FLI-1 to distinguish EWS/PNET from all types of malignancies were 74.2% and 96.0%, respectively. Finally, the sensitivity and specificity of FLI-1 to distinguish EWS/PNET from other small round cell tumours (SRCTs) were 74.2% and 91.6%, respectively. CONCLUSION: This study was the first to show that FLI-1 can be seen in a variety of solid tumours, some of which had never been explored before. This finding should be kept in mind, especially when using FLI-1 as a marker for finding the primary origin of poorly differentiated metastatic tumour. Finally, despite the expression of FLI-1 in numerous malignancies, it is still considered to be highly sensitive and specific in distinguishing EWS/PNET from other tumour types in general and from other SRCTs in particular.

Biomarkers, Tumor↗

PubMed2005

Proteome analysis of early somatic embryogenesis in Picea glauca.

Forestry is a valuable natural resource for many countries. Rapid production of large quantities of genetically improved and uniform seedlings for restocking harvested lands is a key component of sustainable forest management programs. Clonal propagation through somatic embryogenesis has the potential to meet this need in conifers and can offer the added benefit of ensuring consistent seedling quality. Although in commercial use, mass production of conifers through somatic embryogenesis is relatively new and there are numerous biological unknowns regarding this complex developmental pathway. To aid in unravelling the embryo developmental process, two-dimensional electrophoresis was employed to quantitatively assess the expression levels of proteins across four stages of somatic embryo maturation in white spruce (0, 7, 21 and 35 days post abscisic acid treatment). Forty-eight differentially expressed proteins have been identified, which display a significant change in abundance as early as day 7 of embryo development. These proteins are involved in a variety of cellular processes, many of which have not previously been associated with embryo development. The identification of these proteins was greatly assisted by the availability of a substantial expressed sequence tag (EST) resource developed for white, sitka and interior spruce. The combined use of these spruce ESTs in conjunction with GenBank accessions for other plants improved the rate of protein identification from 38% to 62% when compared with GenBank alone using automated, high-throughput techniques. This underscores the utility of EST resources in a proteomic study of any species for which a genome sequence is unavailable.

Cell Line↗

PubMed2006

Tissue microarray analysis of human FRAT1 expression and its correlation with the subcellular localisation of beta-catenin in ovarian tumours.

The mechanisms involved in the pathogenesis of ovarian cancer are poorly understood, but evidence suggests that aberrant activation of Wnt/beta-catenin signalling pathway plays a significant role in this malignancy. However, the molecular defects that contribute to the activation of this pathway have not been elucidated. Frequently rearranged in advanced T-cell lymphomas-1 (FRAT1) is a candidate for the regulation of cytoplasmic beta-catenin. In this study, we developed in situ hybridisation probes to evaluate the presence of FRAT1 and used an anti-beta-catenin antibody to evaluate by immunohistochemistry the expression levels and subcellular localisation of beta-catenin in ovarian cancer tissue microarrays. Expression of FRAT1 was found in some human normal tissues and 47% of ovarian adenocarcinomas. A total of 46% of ovarian serous adenocarcinomas were positive for FRAT1 expression. Accumulation of beta-catenin in the nucleus and/or cytoplasm was observed in 55% ovarian adenocarcinomas and in 59% of serous adenocarcinomas. A significant association was observed in ovarian serous adenocarcinomas between FRAT1 and beta-catenin expression (P<0.01). These findings support that Wnt/beta-catenin signalling may be aberrantly activated through FRAT1 overexpression in ovarian serous adenocarcinomas. The mechanism behind the overexpression of FRAT1 in ovarian serous adenocarcinomas and its significance is yet to be investigated.

Adaptor Proteins, Signal Transducing↗

PubMed2005

Piezoelectric immunochip for the detection of dengue fever in viremia phase.

The global prevalence of dengue fever has grown so dramatically in recent years that it is endemic in more than 100 countries and has become a major international public health concern. Moreover, since the flu-like symptoms that accompany dengue fever are atypical and varied, the detection procedures currently used to identify it are cumbersome and time-consuming, making early stage epidemiological control and effective medical treatment of this epidemic almost impossible. In this study, a QCM-based detection system was developed in which two monoclonal antibodies against dengue E and NS-1 protein, respectively, were control orientated immobilized on QCM via protein A to produce an immunochip. Various sample pretreatment procedures were evaluated to ascertain the most suitable combination, and both the simulating samples and the clinical specimen were examined by the immunochip. The results revealed that the cibacron blue 3GA gel-heat denature (CB-HD) method was the most effective sample pretreatment technique. Due to the complex composition of the serum, the immunochip could only effectively quantify dengue viral antigens in a 1/1000 untreated simulated sample. With the help of the CB-HD method, the dilution folds were found to capable of being reduced from 1000 to 100, and the detection limit lowered to 1.727 microg/ml (E protein) and 0.740 microg/ml (NS-1 protein) in the original sample. While the cocktail immunochip could not quantify both antigens separately, the higher signal level rendered it a more effective qualification tool for suspect screening. Moreover, the results of the analysis of clinical specimens also proved the ability and future potential of cocktail immunochip in discriminating dengue-positive cases from negative serum specimens in the viremia phase.

Adolescent↗

PubMed2002

Tissue microarray molecular profiling of early, node-negative adenocarcinoma of the rectum: a comprehensive analysis.

PURPOSE: Early-stage adenocarcinoma of the rectum treated with curative intent has a favorable overall prognosis; however, 20%-30% of the patients recur, and the majority ultimately die of disease. Recurrence and tumor-related mortality may be attributable to molecular abnormalities in primary tumors accounting for their more aggressive biological behavior. This study evaluates such molecular phenotypes with regard to cell cycle regulation and proliferation and determines their significance for patient outcome. EXPERIMENTAL DESIGN: One hundred patients with primary T(2-3), N(0) adenocarcinoma of the rectum uniformly treated by surgery alone were studied. Core biopsies of pathological specimens were assembled on tissue microarrays, and expression of p53, mdm-2, p21, Bcl-2, p27, cyclin D1, and Ki-67 was analyzed by immunohistochemistry. Molecular profiles were correlated with disease-free (DFS) and disease-specific survival (DSS). RESULTS: Despite previously described prognostic relevance of some of the investigated molecules in analyses where different stages of colorectal cancer were included, none of the cell cycle-regulatory or proliferation-related markers was associated with recurrence or survival. However, patients with tumors demonstrating down-regulation of p27, a cyclin-dependent kinase inhibitor and tumor suppressor gene associated with development of metastases, showed a trend toward reduced DFS and DSS (P = 0.06 and P = 0.07, respectively). CONCLUSIONS: In this homogeneous group of patients with early-stage, node-negative adenocarcinoma of the rectum uniformly treated by surgery alone, the investigated cell cycle-regulatory and proliferation-associated proteins appear to have no prognostic significance. However, down-regulation of p27 appears to be associated with a trend toward reduced DFS and DSS, which suggests further investigation of other p27-related pathways potentially relevant for metastatic disease.

Adenocarcinoma↗

PubMed2006

Identification of Flt3 internal tandem duplications downstream targets by high-throughput immunoblotting protein array system.

The receptor tyrosine kinase Flt3 plays an important role in proliferation and survival of hematopoietic cells. Flt3 is the most frequently mutated gene (20-30%) in cases of acutemyeloid leukemia (AML). The majority of Flt3 mutations are internal tandem duplications (ITD) in the juxtamembrane domain of Flt3 receptor. This mutation results in the constitutive activation of STAT5 and Ras/mitogen-activated protein kinase pathways, leading to the aberrant growth of AML cells. In this study, to better understand the mechanisms of Flt3-ITD to the downstream pathways, a high-throughput immunoblotting protein array system was employed. As a result, c-Jun and c-Raf were markedly induced, suggesting that these factors are functional downstream targets of Flt3-ITD.

Animals↗

PubMed2006

Down-regulation of p21 (CDKN1A/CIP1) is inversely associated with microsatellite instability and CpG island methylator phenotype (CIMP) in colorectal cancer.

p21 (CDKN1A/CIP1/WAF1), one of the cyclin-dependent kinase inhibitors, plays a key role in regulating the cell cycle and is transcriptionally regulated by p53. Down-regulation of p21 is caused by TP53 mutations in colorectal cancer. CpG island methylator phenotype (CIMP) appears to be a distinct subtype of colorectal cancer with concordant methylation of multiple gene promoters and is associated with a high degree of microsatellite instability (MSI-H) and BRAF mutations. However, no study to date has evaluated the relationship between p21 expression and CIMP in colorectal cancer. The purpose of this study was to examine the inter-relationships between p21, p53, CIMP, MSI and KRAS/BRAF status in colorectal cancer. We utilized 737 relatively unbiased samples of colorectal cancers from two large prospective cohort studies. Using quantitative real-time PCR (MethyLight), we measured DNA methylation in five CIMP-specific gene promoters [CACNA1G, CDKN2A (p16/INK4A), CRABP1, MLH1 and NEUROG1]. CIMP-high (>or=4/5 methylated promoters) was diagnosed in 118 (16%) of the 737 tumours. We also assessed expression of p21 and p53 by immunohistochemistry. Among the 737 tumours, 371 (50%) showed p21 loss. Both p21 loss and p53 positivity were inversely associated with CIMP-high, MSI-H and BRAF mutations. The associations of p21 with these molecular features were still present after tumours were stratified by p53 status. In contrast, the associations of p53 positivity with the molecular features were no longer present after tumours were stratified by p21 status. When CIMP-high and non-CIMP-high tumours were stratified by MSI or KRAS/BRAF status, CIMP-high and MSI-H (but not BRAF mutations) were still inversely associated with p21 loss. In conclusion, down-regulation of p21 is inversely correlated with CIMP-high and MSI-H in colorectal cancer, independent of TP53 and BRAF status.

Colorectal Neoplasms↗

PubMed2003

Oxyphilic and non-oxyphilic thyroid carcinoma cell lines differ in expressing apoptosis-related genes.

Oxyphilic tumors of the thyroid are characterized by mitochondrion-rich cells and extensive DNA fragmentation. In order to clarify if a different expression of apoptosis-related genes could be responsible for DNA fragmentation in oxyphilic cell tumors, two thyroid follicular carcinoma-derived cell lines, having oxyphilic (XTC.UC1) and non-oxyphilic (WRO) features, were compared applying a gene array technique. Under basal culture conditions, several pro-apoptotic genes [caspases 3 and 10, Fas and the tumor necrosis factor-related apoptosis-inducing ligand (trail) genes] were switched on in oxyphilic, but not in non-oxyphilic cells. No difference in the mitochondrial apoptosis-related genes (bax, bad, bcl family etc.) was observed. Using the ISEL technique, the extent of DNA fragmentation did not differ under basal conditions in the two cell lines. Conversely, following an oxidative pro-apoptotic stress (6-h methylene blue treatment and light exposure), XTC.UC1 cells showed an extensive DNA fragmentation (up to 70% of cells), dramatically exceeding that observed in WRO cells (up to 20% of cells). In contrast, the oxidative stimulus induced a remarkable apoptosis gene activation in non-oxyphilic WRO cells only. These results suggest that oxyphilic cells may have a unique silent activation of a pro-apoptotic phenotype, which could be responsible for DNA instability and lead to cell death as the consequence of an increased sensitivity to ischemic stresses, as frequently observed in vivo.

Adenocarcinoma↗