Prosurvival function of the granulin-epithelin precursor is important in tumor progression and chemoresponse.


Journal Article

The granulin-epithelin precursor (GEP/PCDGF), a 68-88 kDa secreted glycoprotein, has been shown to be an important growth and survival factor for ovarian cancer cells. Furthermore, GEP expression is a predictor of patient survival in metastatic ovarian cancer cells. Up to this point, however, the molecular mechanisms and clinical relevance of a GEP-mediated prosurvival phenotype remain poorly characterized. We hypothesize that the prosurvival function of GEP is important in ovarian cancer tumor progression and chemoresponse. To explore this hypothesis, we examined the effects of GEP overexpression on migration, invasion and cisplatin (CDDP) chemosensitivity in the ovarian cancer cell line A2780. Full length GEP transfectants demonstrated an increased capacity to migrate and invade their substratum when compared to empty vector controls. In addition, GEP overexpression was associated with CDDP chemoresistance. Finally, GEP overexpression increased tumor formation and protected cells from tumor regression in response to CDDP treatment in vivo. Taken together, these data support a role for GEP in tumor progression and development of drug resistance.

Full Text

Cited Authors

  • Pizarro, GO; Zhou, XC; Koch, A; Gharib, M; Raval, S; Bible, K; Jones, MB

Published Date

  • June 1, 2007

Published In

Volume / Issue

  • 120 / 11

Start / End Page

  • 2339 - 2343

PubMed ID

  • 17266030

Pubmed Central ID

  • 17266030

International Standard Serial Number (ISSN)

  • 0020-7136

Digital Object Identifier (DOI)

  • 10.1002/ijc.22559


  • eng

Conference Location

  • United States