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PubMed2026

Human Wings Apart-Like Protein as a Serum Diagnostic Biomarker in Cervical Cancer: An Integrative Bioinformatics Analysis with Serum Validation.

Cervical cancer remains a major threat to women's health worldwide, and reliable serum biomarkers for early detection and therapeutic stratification remain limited. Human wings-apart-like (hWAPL) protein has been implicated in cervical carcinogenesis, but its diagnostic and clinical value has not been fully elucidated. To address this gap, this study integrated public multi-omics datasets, including The Cancer Genome Atlas, GEPIA2, the Human Protein Atlas, and single-cell transcriptomic data, to characterize hWAPL expression, clinicopathological associations, immune infiltration, co-expression networks, post-translational modifications, and drug sensitivity predictions. These findings were evaluated in an independent single-center serum cohort comprising 89 patients with histologically confirmed cervical squamous cell carcinoma and 89 healthy female controls. Serum hWAPL and squamous cell carcinoma antigen (SCC) levels were measured, and diagnostic performance was assessed by receiver operating characteristic curve analysis. In silico, hWAPL was broadly upregulated across multiple malignancies, particularly cervical cancer, enriched in malignant epithelial cells and monocytes/macrophages, and associated with shorter progression-free interval, predicted reduced sensitivity to cisplatin, paclitaxel, and 5-fluorouracil, and predicted sensitivity to MCL-1 and Wee1 inhibitors. In the serum cohort, hWAPL levels were significantly higher in patients than controls and discriminated cervical cancer with an area under the curve of 0.961, exceeding SCC alone. Combining hWAPL with SCC further improved diagnostic performance (area under the curve, 0.974; sensitivity, 93.3%; specificity, 95.5%). These findings suggest that serum hWAPL is a potential novel diagnostic biomarker for cervical squamous cell carcinoma whose performance is enhanced by SCC, whereas the observed associations with chemoresistance and immune microenvironment remodeling are hypothesis-generating and require experimental confirmation.

Humans↗

PubMed2004

A gene atlas of the mouse and human protein-encoding transcriptomes.

The tissue-specific pattern of mRNA expression can indicate important clues about gene function. High-density oligonucleotide arrays offer the opportunity to examine patterns of gene expression on a genome scale. Toward this end, we have designed custom arrays that interrogate the expression of the vast majority of protein-encoding human and mouse genes and have used them to profile a panel of 79 human and 61 mouse tissues. The resulting data set provides the expression patterns for thousands of predicted genes, as well as known and poorly characterized genes, from mice and humans. We have explored this data set for global trends in gene expression, evaluated commonly used lines of evidence in gene prediction methodologies, and investigated patterns indicative of chromosomal organization of transcription. We describe hundreds of regions of correlated transcription and show that some are subject to both tissue and parental allele-specific expression, suggesting a link between spatial expression and imprinting.

Animals↗

PubMed2005

Antibody-based proteomics for human tissue profiling.

Here, we describe the use of antibody-based proteomics involving the generation of protein-specific antibodies to functionally explore the human proteome. The antibodies can be used for analysis of corresponding proteins in a wide range of assay platforms, including i) immunohistochemistry for detailed tissue profiling, ii) specific affinity reagents for various functional protein assays, and iii) capture ("pull-down") reagents for purification of specific proteins and their associated complexes for structural and biochemical analyses. In this review, the use of antibodies for such analysis will be discussed with focus on the possibility to create a descriptive and comprehensive protein atlas for tissue distribution and subcellular localization of human proteins in both normal and disease tissues.

Antibodies↗

PubMed2026

Spatial proteomic mapping of the human and mouse retina using IBEX.

We generated a comparative spatial proteomic atlas of the human and mouse retina using a highly multiplexed immunohistochemistry technique called iterative bleaching extends multiplexity (IBEX). We refined the IBEX workflow by integrating an antibody dissociation option alongside chemical bleaching. This dual strategy enabled removal of the entire antibody complex, permitting the flexible use of antibodies from the same host species across iterative cycles. We coupled this workflow with super-resolution imaging via deconvolution and applied it to the retina of healthy humans and WT mice and the Crb1rd8 mouse model. We successfully imaged over 25 protein markers on human and mouse tissue sections, generating spatial atlases of the major retinal cell populations. Cross-species protein expression was compared to scRNA-seq datasets to identify protein and transcript disparities. Super-resolution IBEX delineated the ultrastructural features of the outer limiting membrane (OLM), identifying CD44 as a core structural component tightly colocalized with a highly organized F-actin belt within Müller glial endfeet. Using the Crb1rd8 mouse model, disruption of this complex was spatially associated with rosette formation and OLM structural failure. In summary, spatial proteomic atlases of the human and mouse retina were used to reveal insights into the arrangement of major retinal cell populations and OLM structure.

Animals↗

PubMed2005

Towards a human proteome atlas: high-throughput generation of mono-specific antibodies for tissue profiling.

A great need exists for the systematic generation of specific antibodies to explore the human proteome. Here, we show that antibodies specific to human proteins can be generated in a high-throughput manner involving stringent affinity purification using recombinant protein epitope signature tags (PrESTs) as immunogens and affinity-ligands. The specificity of the generated affinity reagents, here called mono-specific antibodies (msAb), were validated with a novel protein microarray assay. The success rate for 464 antibodies generated towards human proteins was more than 90% as judged by the protein array assay. The antibodies were used for parallel profiling of patient biopsies using tissue microarrays generated from 48 human tissues. Comparative analysis with well-characterized monoclonal antibodies showed identical or similar specificity and expression patterns. The results suggest that a comprehensive atlas containing extensive protein expression and subcellular localization data of the human proteome can be generated in an efficient manner with mono-specific antibodies.

Animals↗

PubMed1999

Differential gene expression pattern between normal human trophoblast and choriocarcinoma cell lines: downregulation of heat shock protein-27 in choriocarcinoma in vitro and in vivo.

OBJECTIVE: Our purpose was to identify potential differences in gene expression between normal trophoblast and choriocarcinoma cells. METHODS: The Atlas human cDNA expression array hybridization technique was used to study the gene expression pattern in normal trophoblast and choriocarcinoma cell lines. Furthermore, to confirm heat shock protein-27 (Hsp-27) expression data, reverse transcriptase-PCR (RT-PCR), Western blot, and immunohistochemical analyses were used in vitro with cell lines and in vivo with paraffin sections. RESULTS: The expression of nine genes was strongly different comparing a normal trophoblast cell line with choriocarcinoma cells on the Atlas membranes. Compared to normal trophoblast cells, six genes were upregulated and three were downregulated in choriocarcinoma cells. Furthermore, the downregulation of Hsp-27 in choriocarcinoma cells was confirmed both in vitro with cell lines and in vivo with paraffin sections using RT-PCR, Western blot, and immunohistochemical techniques. CONCLUSION: cDNA expression array is a useful technique for identifying differentially expressed gene patterns in normal trophoblast and choriocarcinoma cells. The strong expression of Hsp-27 in placental villous trophoblast cells may play a role in trophoblast differentiation. The downregulation of Hsp-27 in choriocarcinoma may contribute to the extreme sensitivity of trophoblastic tumors to chemotherapy.

Choriocarcinoma↗

PubMed2026

GWAS Meta-analysis Identifies Novel Associated Loci and Points to Causal Tissues in Central Serous Chorioretinopathy.

OBJECTIVE: To define CSC genetic architecture and identify implicated ocular tissues, cell types, genes, and circulating proteins. DATA SOURCES: Genome-wide data were assembled from FinnGen, All of Us, Mass General Brigham Biobank, Million Veteran Program, and a Dutch chronic CSC cohort. Serum protein quantitative trait loci, human single-cell ocular atlases, and UK Biobank macular optical coherence tomography (OCT) imaging were used for downstream analyses. STUDY SELECTION: Five European-ancestry cohorts with genome-wide data and cohort-specific CSC case-control definitions were included, comprising 2,584 cases and 1,044,455 controls. Variants present in at least 2 cohorts were meta-analyzed. DATA EXTRACTION AND SYNTHESIS: Cohort-level GWASs were adjusted for age, age squared, sex, genotyping array or batch, and 10 genetic principal components, then combined using fixed-effects inverse-variance meta-analysis. Post-GWAS analyses included gene prioritization, colocalization, Mendelian randomization, single-cell disease-relevance scoring, and testing of a CSC genetic risk score in UK Biobank OCT images. MAIN OUTCOMES AND MEASURES: Genome-wide significant CSC loci, effector genes and proteins, tissue and cell-type enrichment, and CSC-relevant OCT abnormalities. RESULTS: Across 11,068,938 variants, 10 loci reached genome-wide significance (P < 5 × 10-8), including 3 novel loci near TGFB1, LINC00551, and LOC105375630 and 7 replicated loci near CFH, CD46, NOTCH4, PREX1, PTPRB, GATA5, and TNFRSF10A. Integrative analyses prioritized 10 candidate effector genes. Colocalization and Mendelian randomization implicated circulating TNFRSF10A, TGFB1, and CASP10 levels. Single-cell analyses localized genetic risk to sclera (P = 2.0 × 10-4) and vascular endothelial cells (P = 4.0 × 10-4), with fibroblast enrichment. In UK Biobank, OCT abnormalities were more frequent in the top vs bottom 1% of CSC genetic risk (18 of 109 [16.5%] vs 8 of 134 [6.0%]; odds ratio, 4.05; 95% CI, 1.65-10.87; P = .002). CONCLUSIONS AND RELEVANCE: In this GWAS meta-analysis, CSC susceptibility localized predominantly to scleral and vascular biology rather than primary retinal pigment epithelial dysfunction. These findings support CSC as a sclerovascular disorder and nominate complement regulation, endothelial signaling, and extracellular matrix pathways for future study.

Journal Article↗

PubMed2005

Atlas - a data warehouse for integrative bioinformatics.

BACKGROUND: We present a biological data warehouse called Atlas that locally stores and integrates biological sequences, molecular interactions, homology information, functional annotations of genes, and biological ontologies. The goal of the system is to provide data, as well as a software infrastructure for bioinformatics research and development. DESCRIPTION: The Atlas system is based on relational data models that we developed for each of the source data types. Data stored within these relational models are managed through Structured Query Language (SQL) calls that are implemented in a set of Application Programming Interfaces (APIs). The APIs include three languages: C++, Java, and Perl. The methods in these API libraries are used to construct a set of loader applications, which parse and load the source datasets into the Atlas database, and a set of toolbox applications which facilitate data retrieval. Atlas stores and integrates local instances of GenBank, RefSeq, UniProt, Human Protein Reference Database (HPRD), Biomolecular Interaction Network Database (BIND), Database of Interacting Proteins (DIP), Molecular Interactions Database (MINT), IntAct, NCBI Taxonomy, Gene Ontology (GO), Online Mendelian Inheritance in Man (OMIM), LocusLink, Entrez Gene and HomoloGene. The retrieval APIs and toolbox applications are critical components that offer end-users flexible, easy, integrated access to this data. We present use cases that use Atlas to integrate these sources for genome annotation, inference of molecular interactions across species, and gene-disease associations. CONCLUSION: The Atlas biological data warehouse serves as data infrastructure for bioinformatics research and development. It forms the backbone of the research activities in our laboratory and facilitates the integration of disparate, heterogeneous biological sources of data enabling new scientific inferences. Atlas achieves integration of diverse data sets at two levels. First, Atlas stores data of similar types using common data models, enforcing the relationships between data types. Second, integration is achieved through a combination of APIs, ontology, and tools. The Atlas software is freely available under the GNU General Public License at: http://bioinformatics.ubc.ca/atlas/

Computational Biology↗

PubMed2005

Cisplatin-induced genes as potential markers for thyroid cancer.

Despite the uncontested role of p53 in cycle arrest/cell death after cisplatin treatment, to date the question whether wild-type p53 confers a resistant or sensitive status on the cell is still a matter of debate. Isogenic and isophenotypic human thyroid papillary carcinoma cell line variants for p53 differently expressed cycle genes after cisplatin treatment. Seven genes (CDC6-related protein, CCNC, GAS1, TFDP2, MAPK10/JNK3, WEE1, RPA1) selected after expression on an Atlas human cell cycle array were analyzed by quantitative real-time PCR. While cisplatin treatment increased their expression in p53 wild-type cells it decreased it in cells with inactivated p53 and had no or less effect on cells with mutated p53. These results show that in a well-defined system, different alterations of p53 can lead to a different regulation of genes and hence to either resistance or sensitivity to cisplatin. Moreover for the first time, MAPK10/JNK3 was identified in human thyroid cells and tissue. Four of the genes (CDC6-related protein, CCNC, GAS1 and TFDP2) were decreased in human papillary carcinoma tissues. Relevance of these genes (especially a decrease in GAS1 in thyroid papillary carcinoma) in various malignant pathologies has already been shown. These genes may be explored as new markers in advanced thyroid cancer such as metastatic and anaplastic forms displaying p53 alterations.

Antineoplastic Agents↗

PubMed2005

The Nuclear Receptor Signaling Atlas: development of a functional atlas of nuclear receptors.

The Nuclear Receptor Signaling Atlas (NURSA) was developed by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute on Aging (NIA), and the National Cancer Institute (NCI) of the National Institutes of Health (NIH); the aim of NURSA is to utilize classical approaches to validate existing hypotheses and exploit new and emerging technologies to formulate and test new hypotheses that might elucidate the program of nuclear receptor (NR) structure, function, and role in disease. The means for carrying out this ambitious program required development of interactions among investigators and the combined application of new high-throughput technologies and existing approaches to allow for both mechanistic studies and accrual of large datasets in a discovery-based research effort, all leading to advances with implications for the missions of the NIDDK, NIA, and NCI. A team-based multidisciplinary approach has allowed for both objectives to proceed simultaneously, tied together via a central bioinformatics resource and one web-accessible venue (www.nursa.org). The ultimate goals for the NURSA consortium are to: 1) establish the mechanistic principles of NR function, 2) characterize NR-coregulator complex formation and regulation, 3) map protein-protein interactions for coregulators, 4) identify candidate downstream target genes of NR action, 5) identify target tissue expression of NRs, 6) understand the regulation of NR expression and, 7) integrate existing and emerging information through NURSA bioinformatics tools.

Animals↗

PubMed2026

Characterizing the Discordance between AT-Rich Interacting Domain 1A Protein and Genotype in Endometrioid-Type Endometrial Tumors.

ARID1A is one of the most frequently mutated genes in endometrial cancer, with approximately 40% of patients harboring an ARID1A mutation. However, relatively little is known about how AT-rich interacting domain 1A (ARID1A) protein loss shapes endometrial cancer pathogenesis. Mounting evidence from other malignancies suggests that ARID1A protein can be regulated post-translationally, independent of genotype. However, most studies in endometrial cancer evaluate genotype alone, overlooking the potential for alternative mechanisms of ARID1A loss. To address this gap, ARID1A protein expression and genotype were examined in endometrioid tumors, and associated transcriptional changes were characterized. Evaluation of ARID1A protein in 71 human endometrioid tumors demonstrates that protein loss can occur regardless of ARID1A genotype. Retention or deficiency of ARID1A protein was not significantly related to variant allele frequency or location of mutation in human tumors with mutant ARID1A. A human endometrial cancer cell model suggests that ARID1A protein loss can occur through proteasomal degradation. Furthermore, ARID1A protein expression was found to be a predictor of worse overall survival in The Cancer Genome Atlas cohort of ARID1A wild-type endometrioid tumors. Spatial transcriptomics of 16 human endometrioid tumors revealed that both genotype and protein expression of ARID1A play a role in shaping unique transcriptional signatures in endometrial cancer and can be used to predict patient prognosis. Suggesting evaluation of ARID1A should not be done solely by sequencing techniques.

Humans↗

PubMed2003

Monocyte chemoattractant protein 3 as a mediator of fibrosis: Overexpression in systemic sclerosis and the type 1 tight-skin mouse.

OBJECTIVE: To determine the gene-expression profile in dermal fibroblasts from type 1 tight-skin (Tsk1) mice, and to examine the expression and potential fibrotic activity of monocyte chemoattractant protein 3 (MCP-3) in Tsk1 mouse and human systemic sclerosis (SSc) skin. METHODS: Complementary DNA microarrays (Atlas 1.2) were used to compare Tsk1 fibroblasts with non-Tsk1 littermate cells at 10 days, 6 weeks, and 12 weeks of age. Expression of MCP-3 protein was assessed by Western blotting of fibroblast culture supernatants, and localized in the mouse and human skin biopsy samples by immunohistochemistry. Activation of collagen reporter genes by MCP-3 was explored in transgenic mouse fibroblasts and by transient transfection assays. RESULTS: MCP-3 was highly overexpressed by neonatal Tsk1 fibroblasts and by fibroblasts cultured from the lesional skin of patients with early-stage diffuse cutaneous SSc. Immunolocalization confirmed increased expression of MCP-3 in the dermis of 4 of 5 Tsk1 skin samples and 14 of 28 lesional SSc skin samples, compared with that in matched healthy mice (n = 5) and human controls (n = 11). Proalpha2(I) collagen promoter-reporter gene constructs were activated by MCP-3 in transgenic mice and by transient transfection assays. This response was maximal between 16 and 24 hours of culture and mediated via sequences within the proximal promoter. The effects of MCP-3 could be diminished by a neutralizing antibody to transforming growth factor beta. CONCLUSION: We demonstrate, for the first time, overexpression of MCP-3 in early-stage SSc and in Tsk1 skin, and suggest a novel role for this protein as a fibrotic mediator activating extracellular matrix gene expression in addition to promoting leukocyte trafficking. This chemokine may be an important early member of the cytokine cascade driving the pathogenesis of SSc.

Adult↗

PubMed2004

An expression atlas of connexin genes in the mouse.

Connexin genes are involved in several human diseases such as hearing and dermatological and peripheral nerve disorders. Connexins are protein units of gap junctions and form homotypic, heterotypic, or heteromeric complexes known as connexons. Data on the expression patterns of members of this family are partial and fragmentary. We therefore cloned all the identifiable murine homologs of human CONNEXIN genes and analyzed their expression patterns in embryonic and neonatal mouse tissues. We found that connexins are preferentially expressed in tissues derived from ectoderm and/or endoderm. Our data provide a comprehensive and detailed atlas of expression of connexin genes and in some cases suggest possible interactions of proteins that are coexpressed in the same tissue. Knowledge of temporal and spatial distribution of connexins also allows the identification of candidate genes for human diseases and provides important insight into mechanisms that lead to human disorders due to mutations in CONNEXIN genes.

Animals↗

PubMed2000

The Morel stereotactic atlas of the human thalamus: atlas-to-MR registration of internally consistent canonical model.

In 1997, Morel, Magnin, and Jeanmonod presented a microscopic stereotactic atlas of the human thalamus. Parcellations of thalamic nuclei did not only use cyto- and myeloarchitectonic criteria, but were additionally corroborated by staining for calcium-binding proteins, which bears functional significance. The atlas complies with the Anglosaxon nomenclature elaborated by Jones and the data were sampled in three orthogonal planes in the AC-PC reference space. We report on the generation of three-dimensional digital models of the thalamus based on the three sets of sections (sagittal, horizontal, and frontal). Spatial differences between the three anatomical specimens were evaluated using the centers of gravity of 13 selected nuclei as landmarks. Subsequent linear regression analysis yielded equations, which were used to normalize the frontal and horizontal digital models to the sagittal one. The outcome is an internally consistent Canonical Model of Morel's atlas, which minimizes the linear component of the variability between the three sectioned anatomical specimens. In addition, we demonstrate the feasibility of the atlas-to-MRI registration in conjunction with on-line visualization of the trajectory in the digital models.

Brain Mapping↗

PubMed1998

CXCR-4, a chemokine receptor, is overexpressed in and required for proliferation of glioblastoma tumor cells.

BACKGROUND AND OBJECTIVES: Using the technique of differential hybridization of Atlas Human cDNA expression arrays, we previously reported the isolation of a G protein coupled receptor, CXCR-4, which is overexpressed in glioblastoma multiforme tumor tissue (GMTT) compared to normal brain tissue (NBT). METHODS: Using gene specific reverse transcriptase-polymerase chain reaction (RT-PCR) and in situ hybridization, we studied its expression in a variety of brain and breast tumor tissue samples. To demonstrate the requirement of CXCR-4 in glioblastoma cell proliferation an antisense construct was overexpressed. Glioblastoma cells were also treated with antibodies against CXCR-4 and its ligand, SDFbeta-1. RESULTS: Expression analysis indicated that CXCR-4 is overexpressed in 57% of the primary glioblastoma tissues and in 88% of the glioblastoma cell lines analyzed. Overexpression of CXCR-4 in glioblastoma cell lines enhanced their soft agar colony-forming capability. Expression of anti-sense CXCR-4 in glioblastoma cell lines caused neurite outgrowth and cellular differentiation. Treatment of glioblastoma cell lines with CXCR-4 and SDFbeta-1 specific antibodies caused inhibition of glioblastoma cell proliferation. CONCLUSIONS: On the basis of these results, we conclude that CXCR-4 gene is required for the proliferation of human glioblastoma tumors.

Brain Neoplasms↗

PubMed1999

OP-1 for cervical spine fusion: bridging bone in only 1 of 4 rheumatoid patients but prednisolone did not inhibit bone induction in rats.

We used OP-1 (also called BMP-7) on a collagen type-1 carrier in atlanto-axial posterior fusions to promote bony healing after wire fixation. 4 patients who had instability between the atlas and axis due to rheumatoid disease received the implants. The patients were examined with conventional radiography postoperatively at 2, 6 and 10 months. In 3 patients, no new bone formation was detectable. In 1 patient, new bone bridged the fusion site at 6 months. 3 patients were on chronic steroid treatment, including the patient in whom bone formation was detected. To determine whether steroid treatment could be responsible for the low rate of bone induction, 24 rats each received OP-1 implants in an abdominal muscle pouch. They were divided into 3 groups receiving saline, 0.1 or 1.0 mg/kg BW of prednisolone daily until they were killed 3 weeks postoperatively. Specimens were decalcified for histology and the amount of calcium in the decalcifying solution was measured. All groups showed ossicles induced by OP-1, and no effect of prednisolone was detected. Thus the failures in the patients may have causes other than prednisolone treatment.

Animals↗

PubMed2025

Single-Cell Splicing Isoform Atlas of the Adult Human Heart and Heart Failure.

BACKGROUND: Alternative splicing plays crucial roles in normal heart development and cardiac disease by influencing protein-coding sequences, functional domains, and molecular networks. However, a detailed characterization of the human heart isoform landscape remains incomplete. METHODS: Leveraging long-read single-nucleus RNA sequencing and computational analysis, we dissected full-length isoform heterogeneities, expression patterns, and usage shifts across cell types, cell states, and cardiac conditions of the adult left ventricle. We applied in silico approaches to assess the functional relevance of identified isoforms; validated isoform compositions of representative cardiac genes using reverse transcription quantitative polymerase chain reaction and targeted amplicon sequencing; and developed a web server for interactive navigation of our results. RESULTS: The data revealed that isoform heterogeneity is widespread in the cardiac cellular system, serving as a posttranscriptional buffer mechanism that calibrates the molecule reservoirs in human hearts. In healthy left ventricles, ≈30% of cell type-specific genes were polyform, using multiple isoforms tailored to cell type-specific programs. Among ubiquitously expressed genes, >300 showed differential isoform usage with cell type specificity in normal hearts. Comparisons of cardiomyocytes across conditions uncovered 379 genes with marked isoform usage shifts, most of which are predicted to change protein coding outcomes through direct changes in protein coding sequences and switches between intron retention and non-protein-coding biotypes. In contrast, cell state-specific programs tend to operate on monoform genes associated with changes among cell states. In addition, our data revealed heart failure-associated differential isoform usage events in stromal and immune cell types in the cardiac microenvironment. CONCLUSIONS: We present a comprehensive atlas of splicing isoforms in the normal adult heart and heart failure through long-read single-nucleus RNA sequencing and computational analyses. The results suggest crucial roles of isoforms in buffering core cellular programs and contributing to disease-associated cell states. The full-length details of these cell-specific isoforms serve as an important reference for downstream translational and mechanistic studies and are available on our online data portal at https://github.com/gaolabtools/heart-isoform-atlas.

Humans↗

PubMed2001

Expression profile of protein tyrosine kinase genes in human osteoarthritis chondrocytes.

OBJECTIVE: To determine the expression profile of protein kinase (PK) and protein tyrosine kinase (PTK) genes in human primary osteoarthritis (OA) chondrocytes and to compare it with that of immortalized human chondrocytes T/C 28a4 with a view to learning whether T/C 28a4 cells can be used for elucidating signal transduction pathways in human chondrocytes. DESIGN: We used the Atlas Human cDNA Array and a method based on PCR with degenerate primers to analyse the expression profile of protein kinase genes in primary human OA chondrocytes and compared it with that of immortalized human chondrocyte cell line T/C 28a4 using RT-PCR and Western blotting. RESULTS: A total of 21 PTK genes were identified and several of these have never been shown to be expressed in human OA chondrocytes. Comparative expression analysis of some selected kinase genes showed that the mRNA expression pattern of many protein kinase genes in OA chondrocytes was identical to that of T/C 28a4 cells. However, there were differences in the level of protein expression of selected protein kinases in these cells. For example, mRNA expression of the novel kinase HCK was detected in OA chondrocytes and in the cell lines analysed but by Western blotting HCK protein was not detected in OA chondrocytes. In these studies, we also identified a novel mutant form of the discoidin domain receptor 2 (DDR2) transcript from chondrocyte-like cell line HTB-94. CONCLUSIONS: Our results provide novel information about protein kinase gene expression in OA chondrocytes and indicate that the transformed chondrocyte cell line T/C 28a4 may be suitable for elucidating signal transduction pathways in chondrocytes and to investigate how they regulate chondrocyte function in inflammatory and degenerative joint diseases.

Blotting, Western↗