This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bonafé, N. Articles by Chambers, S. K. Search for Related Content PubMed PubMed Citation Articles by Bonafé, N. Articles by Chambers, S. K.

Glyceraldehyde-3-Phosphate Dehydrogenase Binds to the AU-Rich 3' Untranslated Region of Colony-Stimulating Factor–1 (CSF-1) Messenger RNA in Human Ovarian Cancer Cells: Possible Role in CSF-1 Posttranscriptional Regulation and Tumor Phenotype

Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Yale University School of Medicine, New Haven, Connecticut

Corresponding author: Setsuko K. Chambers, Arizona Cancer Center, University of Arizona, P.O. Box 245024, Tucson, AZ 85724-5024. Phone: 520-626-0950; Fax: 520-626-8574; E-mail: schambers{at}azcc.arizona.edu.

The overexpression of the colony-stimulating factor–1(CSF-1) by epithelial ovarian cancer cells enhances invasiveness and metastatic properties, contributing to the poor prognosis of the patients. It has been suggested that CSF-1 3' untranslated region containing AU-rich elements (ARE) could regulate CSF-1 posttranscriptional expression and be responsible for its aberrant abundance in such cancer cells. In this study, normal (NOSE.1) and malignant (Hey) ovarian epithelial cells were used to examine CSF-1 expression and regulation. CSF-1 overexpression in Hey cells was found to associate with increased invasiveness, motility, urokinase activity, and virulence of tumorigenicity, compared with NOSE.1 cells, which expressed little CSF-1. CSF-1 ARE was further found to serve as an mRNA decay element that correlates with down-regulation of protein translation. Moreover, such down-regulation was found more prominent in NOSE.1 than in Hey cells, suggesting differences in posttranscriptional regulation. As a variety of trans-acting factors [AU-binding protein (AUBP)] are known to modulate messenger stability through binding to such elements, we examined the protein content of both cell lines for their ability to bind the CSF-1 ARE. Our results strongly suggested the abundance of such AUBP activity in Hey cells. We isolated a 37-kDa AUBP, which was identified as glyceraldehyde-3-phosphate dehydrogenase (GAPDH).

To summarize, our study identified GAPDH as an AUBP abundant in Hey cells, where it binds to CSF-1 ARE that imparts mRNA decay. These data suggest that GAPDH binding to CSF-1 ARE sequence prevents CSF-1 mRNA decay and subsequent down-regulation of CSF-1 protein translation, leading to CSF-1 overexpression and increased metastatic properties seen in ovarian cancer.

This article has been cited by other articles:

				M. A. Edson, A. K. Nagaraja, and M. M. Matzuk The Mammalian Ovary from Genesis to Revelation Endocr. Rev., October 1, 2009; 30(6): 624 - 712. [Abstract] [Full Text] [PDF]

				M. Backlund, K. Paukku, L. Daviet, R. A. De Boer, E. Valo, S. Hautaniemi, N. Kalkkinen, A. Ehsan, K. K. Kontula, and J. Y. A. Lehtonen Posttranscriptional regulation of angiotensin II type 1 receptor expression by glyceraldehyde 3-phosphate dehydrogenase Nucleic Acids Res., April 1, 2009; 37(7): 2346 - 2358. [Abstract] [Full Text] [PDF]

				K. M. Irvine, M. R. Andrews, M. A. Fernandez-Rojo, K. Schroder, C. J. Burns, S. Su, A. F. Wilks, R. G. Parton, D. A. Hume, and M. J. Sweet Colony-stimulating factor-1 (CSF-1) delivers a proatherogenic signal to human macrophages J. Leukoc. Biol., February 1, 2009; 85(2): 278 - 288. [Abstract] [Full Text] [PDF]

				F. Rodriguez-Pascual, M. Redondo-Horcajo, N. Magan-Marchal, D. Lagares, A. Martinez-Ruiz, H. Kleinert, and S. Lamas Glyceraldehyde-3-Phosphate Dehydrogenase Regulates Endothelin-1 Expression by a Novel, Redox-Sensitive Mechanism Involving mRNA Stability Mol. Cell. Biol., December 1, 2008; 28(23): 7139 - 7155. [Abstract] [Full Text] [PDF]

				Y. Zhou, X. Yi, J. B. Stoffer, N. Bonafe, M. Gilmore-Hebert, J. McAlpine, and S. K. Chambers The Multifunctional Protein Glyceraldehyde-3-Phosphate Dehydrogenase Is Both Regulated and Controls Colony-Stimulating Factor-1 Messenger RNA Stability in Ovarian Cancer Mol. Cancer Res., August 1, 2008; 6(8): 1375 - 1384. [Abstract] [Full Text] [PDF]

				G. Castellano, J. F. Reid, P. Alberti, M. L. Carcangiu, A. Tomassetti, and S. Canevari New Potential Ligand-Receptor Signaling Loops in Ovarian Cancer Identified in Multiple Gene Expression Studies Cancer Res., November 15, 2006; 66(22): 10709 - 10719. [Abstract] [Full Text] [PDF]

				X. Lu, L. de la Pena, C. Barker, K. Camphausen, and P. J. Tofilon Radiation-Induced Changes in Gene Expression Involve Recruitment of Existing Messenger RNAs to and away from Polysomes Cancer Res., January 15, 2006; 66(2): 1052 - 1061. [Abstract] [Full Text] [PDF]