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Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

ABSTRACT: Cyclophilin B (CypB) is a 21-kDa protein with peptidyl-prolyl cis-trans isomerase activity that functions as a transcriptional inducer for Stat5 and as a ligand for CD147. To better understand the global function of CypB in breast cancer, T47D cells with a small interfering RNA-mediated knockdown of CypB were generated. Subsequent expression profiling analysis showed that 663 transcripts were regulated by CypB knockdown, and that many of these gene products contributed to cell proliferation, cell motility, and tumorigenesis. Real-time PCR confirmed that STMN3, S100A4, S100A6, c-Myb, estrogen receptor alpha, growth hormone receptor, and progesterone receptor were all down-regulated in si-CypB cells. A linkage analysis of these array data to protein networks resulted in the identification of 27 different protein networks that were impacted by CypB knockdown. Functional assays demonstrated that CypB knockdown also decreased cell growth, proliferation, and motility. Immunohistochemical and immunofluorescent analyses of a matched breast cancer progression tissue microarray that was labeled with an anti-CypB antibody demonstrated a highly significant increase in CypB protein levels as a function of breast cancer progression. Taken together, these results suggest that the enhanced expression of CypB in malignant breast epithelium may contribute to the pathogenesis of this disease through its regulation of the expression of hormone receptors and gene products that are involved in cell proliferation and motility.

SUBMITTER: Fang F

PROVIDER: S-EPMC2631342 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

Fang Feng F Flegler Ayanna J AJ Du Pan P Lin Simon S Clevenger Charles V CV

The American journal of pathology 20081204 1

Cyclophilin B (CypB) is a 21-kDa protein with peptidyl-prolyl cis-trans isomerase activity that functions as a transcriptional inducer for Stat5 and as a ligand for CD147. To better understand the global function of CypB in breast cancer, T47D cells with a small interfering RNA-mediated knockdown of CypB were generated. Subsequent expression profiling analysis showed that 663 transcripts were regulated by CypB knockdown, and that many of these gene products contributed to cell proliferation, cel ...[more]

PMID: 19056847

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Project description:Background The genes and genetic mechanisms underlying the occurrence and progression of papillary thyroid carcinoma (PTC) are still unknown. This study aimed to find candidate genes related to the pathogenesis and progression of PTC. Methods RNA sequencing (RNA-seq) data of PTC and normal tissues were downloaded from The Cancer Genome Atlas (TCGA) database with clinical stage data to form a test, validation, and clinical-stage data matrix. We used the test data set to analyze differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA) to find those gene clusters highly correlated with PTC. We then verified the expression of genes in the interested modules using the validation matrix. The quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the reliability of the expression of selected genes. Five key genes (GDF15, LCN2, KCNN4, SH3BGRL3, and MMP2) were used to analyze the connection between gene expression and the American Joint Committee on Cancer (AJCC) stage. The upregulated and downregulated DEGs, along with the modules of interest, were subjected to Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Results We used WGCNA to find two modules of interest, the yellow module, which was positively associated with PTC, and the blue module, which was negatively correlated with PTC. Four genes (GDF15, LCN2, KCNN4, and SH3BGRL3) from the yellow module were determined to be highly expressed in PTC in the test data matrix and were verified in both the validation data matrix and quantitative real-time PCR, which indicated that these four genes were highly correlated with the occurrence of the PTC. Furthermore, these four genes also had a significantly higher expression in the advanced levels of pathological T, N, and AJCC stage, meaning that they were correlated with the progression of PTC. Genes in the yellow module and upregulated DEGs were significantly enriched in three vital signaling pathways, including focal adhesion, extracellular matrix (ECM)-receptor interaction, and the PI3K-Akt signaling pathway. Conclusions Four candidate genes (GDF15, LCN2, KCNN4, and SH3BGRL3) may be potential biomarkers for the PTC’s pathogenesis and may be useful for predicting the disease stage.

Dataset Information

Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

Publications

Expression of cyclophilin B is associated with malignant progression and regulation of genes implicated in the pathogenesis of breast cancer.

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