Gene Expression Alterations in Prostate Cancer Predicting Tumor Aggression and Preceding Development of Malignancy

Yu, Yan; Landsittel, Douglas; Jing, Ling; Nelson, Joel B.; Ren, B; Liu, Lijun; McDonald, Courtney; Thomas, Ryan M.; Dhir, Rajiv; Finkelstein, Sydney; Michalopoulos, George K.; Becich, Michael J.; Luo, Jianhua

doi:10.1200/jco.2004.05.158

Cited by 664 publications

(601 citation statements)

References 18 publications

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“…1a) in a public database. 10 Consistently, Tpl2 mRNA expression in human ADI PC cells PC3, DU145 and C4-2B cells, which exhibit in vivo tumorigenic/ metastatic potential, was higher than that in the weakly tumorigenic/nonmetastatic 22Rv1 human ADI PC cells (Supporting Information Fig. 1b).…”

Section: Tpl2 Enhances In Vivo Tumorigenesis and Metastasis Of Adi Pcsupporting

confidence: 54%

“…10,14,15,39 However, the expected changes in ERK and JNK phosphorylation were not induced by either downregulation or overexpression of Tpl2 in ADI PC cells in this study although the mechanisms underlying the differential Tpl2-mediated downstream signaling was not elucidated in detail. Instead, upregulation of FAK and CXCR4 and activation of FAK/Akt and CXCL12/CXCR4 signaling pathways were associated with Tpl2 expression in ADI PC cells.…”

Section: Discussionmentioning

confidence: 57%

“…[10][11][12] Previously, we reported that Tpl2 is a novel oncogene linked to the disease progression and metastasis of clear cell renal cell carcinoma (ccRCC). 13 Intriguingly, Tpl2 is a key signal transducer of arsenite, which is a critical risk factor of PC.…”

mentioning

confidence: 99%

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Tpl2 induces castration resistant prostate cancer progression and metastasis

Lee

Cho

Lee

et al. 2014

Intl Journal of Cancer

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Progression to metastatic castration resistant prostate cancer (CRPC) is the major lethal pathway of prostate cancer (PC). Herein, we demonstrated that tumor progression locus 2 (Tpl2) kinase is the fundamental molecule provoking progression and metastasis of CRPC. Tpl2 upregulates CXCR4 and focal adhesion kinase (FAK) to activate CXCL12/CXCR4 and FAK/Akt signalling pathway. Consequently, epithelial-mesenchymal transition (EMT) and stemness of androgen depletion independent (ADI) PC cells are induced, which is dependent on the kinase activity of Tpl2. In vitro, proliferation, clonogenicity, migration, invasion and chemoresistance of ADI PC cells were enhanced by Tpl2. In vivo, Tpl2 overexpression and downregulation showed significant stimulatory and inhibitory effects on tumorigenic and metastatic potential of ADI PC cells, respectively. Moreover, the prognostic effects of Tpl2 and expressional correlation between Tpl2 and EMT-related molecules/CXCR4 were validated in clinical PC databases. Since Tpl2 exerts metastatic progression promoting activities in CRPC, Tpl2 could serve as a novel therapeutic target for metastatic CRPC.Prostate cancer (PC) is the most common cancer and second leading cause of cancer-related deaths in males in the United States. 1 Although androgen depletion therapy is highly effective in suppressing PC growth, persistent androgen ablation often results in the development of metastatic castration resistant prostate cancer (CRPC). 2 Currently, patients with metastatic CRPC are treated with taxane-based chemotherapeutic drugs. However, the treatment only serves as a palliative, and distant metastasis is the main cause of PC-related death. 3 Therefore, the identification of novel therapeutic targets in metastatic CRPC is the most urgent clinical requirement that remains unmet.Tumors contain a reservoir of cancer stem cells (CSCs) that are responsible for tumor initiation, progression, metastasis and therapeutic resistance. 4 Since emerging evidence suggests that PC CSCs represent the "bad seeds" of tumor, the molecular mechanisms that maintain PC CSCs could potentially serve as therapeutic targets for metastatic CRPC. 5,6 Although aldehyde dehydrogenase (ALDH) activity 7 and expression of CD44 8 and Bmi-1 9 have been suggested as specific PC CSC markers, using these markers as therapeutic targets is challenging because the molecules lack specific functional and/or enzymatic activities.Tumor progression locus 2 [Tpl2/MAP3 kinase 8 (MAP3K8)], a serine/threonine protein kinase, has been suggested to enhance tumor growth and metastatic progression in distinct types of human cancers. 10-12 Previously, we

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Section: Tpl2 Enhances In Vivo Tumorigenesis and Metastasis Of Adi Pcsupporting

confidence: 54%

Section: Discussionmentioning

confidence: 57%

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Tpl2 induces castration resistant prostate cancer progression and metastasis

Lee

Cho

Lee

et al. 2014

Intl Journal of Cancer

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“…Further, there now exists some evidence to support the observation that molecular alterations occur in non-cancerous tissues surrounding cancer foci in the prostate. In one study, Yu et al 41 performed comprehensive gene expression analysis on PCa tissues, prostate tissues adjacent to cancer foci and organ donor prostates. They identified 1022 genes that were differentially expressed in prostate tissues adjacent to tumors compared with organ donor prostates.…”

Section: Discussionmentioning

confidence: 99%

Androgen receptor CAG repeat length contraction in diseased and non-diseased prostatic tissues

Sircar

Gottlieb

Alvarado

et al. 2007

Prostate Cancer Prostatic Dis

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“…The test data has two advantages over real data: we have total control of which genes are differentially expressed for identifying true and false positives, and we have total control of the appearance and location of artifacts. To simulate conditions observed in real array experiments as much as possible, real values from real arrays 25 are used to construct the test data. Some data are harvested from obvious regions of artifact as well as from regions determined to be generally artifact free.…”

Section: Generation Of Test Datamentioning

confidence: 99%

chip artifact CORRECTion (caCORRECT): A Bioinformatics System for Quality Assurance of Genomics and Proteomics Array Data

2007

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Abstract-Quality assurance of high throughput ''-omics'' data is a major concern for biomedical discovery and translational medicine, and is considered a top priority in bioinformatics and systems biology. Here, we report a webbased bioinformatics tool called caCORRECT for chip artifact detection, analysis, and CORRECTion, which removes systematic artifactual noises that are commonly observed in microarray gene expression data. Despite the development of major databases such as GEO arrayExpress, caArray, and the SMD to manage and distribute microarray data to the public, reproducibility has been questioned in many cases, including high-profile papers and datasets. Based on both archived and synthetic data, we have designed the caCORRECT to have several advanced features: (1) to uncover significant, correctable artifacts that affect reproducibility of experiments; (2) to improve the integrity and quality of public archives by removing artifacts; (3) to provide a universal quality score to aid users in their selection of suitable microarray data; and (4) to improve the truepositive rate of biomarker selection verified by test data. These features are expected to improve the reproducibility of Microarray study. caCORRECT is freely available at: http:// caCORRECT.bme.gatech.edu.

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Gene Expression Alterations in Prostate Cancer Predicting Tumor Aggression and Preceding Development of Malignancy

Abstract: We also found that gene expression patterns can be used to predict the aggressiveness of prostate cancer using a novel model.

Cited by 664 publications

References 18 publications

Tpl2 induces castration resistant prostate cancer progression and metastasis

Tpl2 induces castration resistant prostate cancer progression and metastasis

Androgen receptor CAG repeat length contraction in diseased and non-diseased prostatic tissues

chip artifact CORRECTion (caCORRECT): A Bioinformatics System for Quality Assurance of Genomics and Proteomics Array Data

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