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Tumor Biology

, Volume 37, Issue 3, pp 2909–2924 | Cite as

The roles of parafibromin expression in ovarian epithelial carcinomas: a marker for differentiation and prognosis and a target for gene therapy

  • Dao-fu Shen
  • Xin Liu
  • Xue-feng Yang
  • Lei Fang
  • Yang Gao
  • Shuang Zhao
  • Ji-cheng Wu
  • Shuai Shi
  • Jun-jun Li
  • Xiang-xuan Zhao
  • Wen-feng Gou
  • Hua-chuan Zheng
Original Article

Abstract

Parafibromin is a protein encoded by hyperparathyroidism 2 (HRPT2) and its downregulated expression is involved in the pathogenesis of parathyroid, breast, gastric, colorectal, lung, head and neck cancers. We aimed to investigate the roles of parafibromin expression in tumorigenesis, progression, or prognostic evaluation of ovarian cancers. HRPT2-expressing plasmid was transfected into ovarian cancer cells with the phenotypes and related molecules examined. The messenger RNA (mRNA) and protein expression of parafibromin were also examined in ovarian normal tissue, benign and borderline tumors and cancers by reverse transcription-polymerase chain reaction (RT-PCR), Western blot, or immunohistochemistry respectively. It was found that parafibromin overexpression caused a lower growth, migration and invasion, higher sensitivity to cisplatin and apoptosis than the mock and control (P < 0.05). The transfectants showed the hypoexpression of phosphoinositide 3-kinase (PI3K), Akt, p70 ribosomal protein S6 kinase (p70s6k), Wnt5a, B cell lymphoma-extra large (Bcl-xL), survivin, vascular endothelial growth factor (VEGF) and matrix metallopeptidase 9 (MMP-9) than the mock and control at both mRNA and protein levels (P < 0.05). According to real-time PCR, parafibromin mRNA level was lower in ovarian benign tumors and cancers than normal ovary (P < 0.05), while parafibromin was strongly expressed in metastatic cancers in omentum than primary cancers by Western blot. Immunohistochemically, parafibromin expression was stronger in primary cancers than that in ovarian normal tissue (P < 0.05) but weaker than the metastatic cancers (P < 0.05) with a positive correlation with dedifferentiation, ki-67 expression and the lower cumulative survival rate (P < 0.05). These findings indicate that parafibromin downregulation might promote the pathogenesis, dedifferentiation and metastasis of ovarian cancers possibly by suppressing aggressive phenotypes, such as proliferation, cell cycle, apoptosis, migration and invasion.

Keywords

Ovarian cancer Parafibromin Pathogenesis Progression Gene therapy 

Notes

Acknowledgments

This study was supported by President Fund of Liaoning Medical University (XZJJ20140201; XZJJ20140203), a project supported by Scientific Research Fund of Liaoning Provincial Education Department (LJQ2014093), a Key Scientific and Technological Project of Liaoning Province (2015408001), and National Natural Scientific Foundation of China (81172371; 81472544).

Conflicts of interest

None

Supplementary material

13277_2015_4103_MOESM1_ESM.docx (16 kb)
Supplementary Table 1 (DOCX 16 kb)
13277_2015_4103_MOESM2_ESM.docx (14 kb)
Supplementary Table 2 (DOCX 14 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Dao-fu Shen
    • 1
  • Xin Liu
    • 2
  • Xue-feng Yang
    • 1
  • Lei Fang
    • 1
  • Yang Gao
    • 1
  • Shuang Zhao
    • 1
  • Ji-cheng Wu
    • 1
  • Shuai Shi
    • 1
  • Jun-jun Li
    • 1
  • Xiang-xuan Zhao
    • 1
  • Wen-feng Gou
    • 1
  • Hua-chuan Zheng
    • 1
  1. 1.Cancer Center, Key Laboratory of Brain and Spinal Cord Injury of Liaoning Province, and Laboratory Animal CenterThe First Affiliated Hospital of Liaoning Medical UniversityJinzhouChina
  2. 2.Department of Clinical LaboratoryThe First Affiliated Hospital of Liaoning Medical UniversityJinzhouChina

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