Journal
GYNECOLOGIC ONCOLOGY
Volume 134, Issue 2, Pages 364-371Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2014.05.025
Keywords
Cervical cancer; Progranulin; Cell proliferation; Transformation
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Funding
- National Natural Science Foundation of China [81102229, 81101980, 81272209, 81300384]
- Natural Science Foundation of Shandong Province [ZR2010HQ001, ZR2012HM031]
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Objective. The growth factor progranulin (PGRN) is overexpressed in a number of tumors. We aimed to investigate the expression and role of PGRN in cervical cancer tumorigenesis. Methods. PGRN expression and secretion was assessed in cells and normal and cancerous cervical tissues by Western blot analysis, ELISA or immunohistochemistry. The role of PGRN in cervical carcinogenesis was explored by cell-proliferation, colony-formation and tumor-growth assays. We assessed the role of PGRN-mediated signaling in the cervical cell with specific inhibitors. Results. PGRN expression was upregulated in cervical cancer cell lines and tissue. PGRN promoted the transformation of human cervical mucosa epithelial H8 cells in vitro and tumor formation in vivo. Knockdown of PGRN expression in cervical cancer cells in vivo decreased cell proliferation and slowed tumor growth. PGRN stimulated cervical cell proliferation, and transformation was mediated, at least in part, by Akt and Erk signaling. Conclusions. PGRN is overexpressed in cervical cancer and promotes the malignant growth and transformation of cervical cells. Therefore, PGRN plays a critical role in carcinogenesis of cervical cancer and shows promise for therapeutic strategies for cervical cancer. (C) 2014 Elsevier Inc. All rights reserved.
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