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The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma

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Abstract

The ubiquitin proteasome pathway has been implicated in carcinogenesis. However, the role of E2-EPF ubiquitin carrier protein (UCP) in esophageal cancer remains relatively unstudied. In the study, we examined the mRNA level of circulating tumor cells from 60 esophageal cancer patients by membrane arrays consisting of a panel of potential markers including UCP, compared to 40 normal populations. The predictive capacity of UCP was also assessed by immunohistochemical staining of a retrospective series of 84 biopsied esophageal squamous cell carcinomas in relation to clinical outcome. In addition, we studied in vitro biological changes including tumor growth, metastatic capacity, and the sensitivity to irradiation and cisplatin, after experimental manipulation of UCP expression in esophageal cancer cells. By the data of 25-gene membrane array analysis, UCP was the only factor significantly associated with the extent of tumor burden in esophageal cancer patients. Our immunochemistry findings further indicate that UCP positivity was linked to poor response to neoadjuvant therapy and worse survival. In cell culture, inhibited UCP significantly decrease tumor growth and the capacity for metastasis. The epithelial–mesenchymal transition (EMT) induced by VHL/HIF-1α-TGF-β1 pathway might be the underlying mechanism responsible to the more aggressive tumor growth in UCP-positive esophageal cancer. Our results suggest that UCP was significantly associated with poor prognosis of esophageal cancer and may be a new molecular target for therapeutic intervention for esophageal squamous cell carcinoma.

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Abbreviations

UCP:

E2-EPF ubiquitin carrier protein

EMT:

Epithelial–mesenchymal transition

VHL:

Von Hippel–Lindau gene

HIF-1α:

Hypoxia-inducible factor-1α

TGF-β1:

Transforming growth factor-beta 1

VEGF:

Vascular endothelial growth factor

EGFR:

Epidermal growth factor receptor

HGF:

Hepatocyte growth factor

PDGF:

Platelet-derived growth factor

TS:

Thymidylate synthase

ERCC1:

Excision repair cross-complementation group 1

SIRT1:

The human homolog of the S. cerevisiae Sir2 protein

PRDX-1:

Peroxiredoxin I

COX-2:

Cycloxygenase-2

ISG15:

Interferon-stimulated gene 15

TOP-1:

Topoisomerase I

TOP-2:

Topoisomerase IIa

CK:

cytokeratin

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Authors and Affiliations

  1. Department of Radiation Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan

    Miao-Fen Chen & Wen-Cheng Chen

  2. Chang Gung Institute of Technology, Chia-yi Campus, Chiayi, Taiwan

    Miao-Fen Chen, Kuan-Der Lee & Wen-Cheng Chen

  3. Department of Medical Oncology, Chang Gung Memorial Hospital, Chiayi, Taiwan

    Kuan-Der Lee & Chih-Cheng Chen

  4. Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Chiayi, Taiwan

    Ming-Shian Lu

  5. Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital, Linko, Taiwan

    Ming-Ju Hsieh & Yun-Hen Liu

  6. Department of Pathology, Chang Gung Memorial Hospital, Chiayi, Taiwan

    Paul-Yang Lin

  7. Chang-Gung Memorial Hospital, Chia-Yi, #6, Chia-Pu Rd., Putz City, Chia-Yi Hsien, Taiwan

    Miao-Fen Chen & Wen-Cheng Chen

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  1. Miao-Fen Chen
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Correspondence to Miao-Fen Chen.

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Chen, MF., Lee, KD., Lu, MS. et al. The predictive role of E2-EPF ubiquitin carrier protein in esophageal squamous cell carcinoma. J Mol Med 87, 307–320 (2009). https://doi.org/10.1007/s00109-008-0430-3

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  • DOI: https://doi.org/10.1007/s00109-008-0430-3

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