title: Inhibition of PC cell-derived growth factor (PCDGF)/granulin-epithelin precursor (GEP) decreased cell proliferation and invasion through downregulation of cyclin D and CDK4 and inactivation of MMP-2.
abstract: BACKGROUND
  PC cell-derived growth factor (PCDGF), also called epithelin/granulin precursor (GEP), is an 88-kDa secreted glycoprotein with the ability to stimulate cell proliferation in an autocrine fashion. In addition, some studies indicated that PCDGF participated in invasion, metastasis and survival of cancer cells by regulating cell migration, adhesion and proliferation. Yet the effects of PCDGF on proliferation and invasion of ovarian cancer cells in vitro and the mechanisms by which PCDGF mediates biological behaviors of ovarian cancer have rarely been reported. In the present study we investigated whether and how PCDGF/GEP mediated cell proliferation and invasion in ovarian cancer.
  
  
  METHODS
  PCDGF/GEP expression level in three human ovarian cancer cell lines of different invasion potential were detected by RT-PCR and western blot. Effects of inhibition of PCDGF expression on cell proliferation and invasion capability were determined by MTT assay and Boyden chamber assay. Expression levels of cyclin D1 and CDK4 and MMP-2 activity were evaluated in a pilot study.
  
  
  RESULTS
  PCDGF mRNA and protein were expressed at a high level in SW626 and A2780 and at a low level in SKOV3. PCDGF expression level correlated well with malignant phenotype including proliferation and invasion in ovarian cancer cell lines. In addition, the proliferation rate and invasion index decreased after inhibition of PCDGF expression by antisense PCDGF cDNA transfection in SW626 and A2780. Furthermore expression of CyclinD1 and CDK4 were downregulated and MMP-2 was inactivated after PCDGF inhibition in the pilot study.
  
  
  CONCLUSIONS
  PCDGF played an important role in stimulating proliferation and promoting invasion in ovarian cancer. Inhibition of PCDGF decreased proliferation and invasion capability through downregulation of cyclin D1 and CDK4 and inactivation of MMP-2. PCDGF could serve as a potential therapeutic target in ovarian cancer.
authors.affiliation: Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China. doctorlyl@yahoo.com.cn <doctorlyl@yahoo.com.cn>
authors.forename: Yulan
authors.initials: Y
authors.lastname: Liu
authors.forename: Ling
authors.initials: L
authors.lastname: Xi
authors.forename: Guoning
authors.initials: G
authors.lastname: Liao
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xun
authors.initials: X
authors.lastname: Tian
authors.forename: Beibei
authors.initials: B
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Han
authors.forename: Mingfu
authors.initials: M
authors.lastname: Wu
authors.forename: Shixuan
authors.initials: S
authors.lastname: Wang
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Yunping
authors.initials: Y
authors.lastname: Lu
authors.forename: Ding
authors.initials: D
authors.lastname: Ma
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition; D049109:Cell Proliferation; D056741:Cyclin D; D051358:Cyclin-Dependent Kinase 4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D016213:Cyclins / Q000037:antagonists & inhibitors* / Q000235:genetics; D016373:DNA, Antisense / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D006131:Growth Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D000077153:Progranulins; D011498:Protein Precursors / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D056741:Cyclin D; D016213:Cyclins; D016373:DNA, Antisense; C492314:GRN protein, human; D006131:Growth Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D061965:Matrix Metalloproteinase Inhibitors; D000077153:Progranulins; D011498:Protein Precursors; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D020778:Matrix Metalloproteinase 2