QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services 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 Doucette, M. M. Articles by Stevens, V. L. Search for Related Content PubMed PubMed Citation Articles by Doucette, M. M. Articles by Stevens, V. L.

---

Biochemical and Molecular Action of Nutrients

Folate Receptor Function Is Regulated in Response to Different Cellular Growth Rates in Cultured Mammalian Cells^{1 ,2}

Division of Cancer Biology, Department of Radiation Oncology, Emory University School of Medicine, Atlanta, GA 30335

³To whom correspondence should be addressed. E-mail: vlsteve{at}emory.edu .

ABSTRACT

The folate receptor (FR) binds physiologic folates with nmol/L affinities and is expected to play an important role in transporting serum folates into cells that express this receptor. Although it has been shown that FR expression increases when extracellular levels of folate are low, whether this receptor is regulated in response to altered cellular requirements for folates or by intracellular levels of this vitamin has not been investigated. In this study, FR levels, FR function and cellular folate levels were measured in cells with different growth rates to investigate FR regulation of this receptor under conditions in which cellular requirements for folate are altered. These experiments used cells that endogenously express FR (JAR, Caco-2 and MA-104) and cells stably transfected with this receptor (FRGPI-16 and FRTM-8). FR function decreased as cellular growth slowed in four of the five cell lines examined. Although cellular folate levels also decreased as cells reached confluence, the total amount of cellular folate in the culture remained constant, suggesting the depleted cellular folate was because of the cell partitioning its pool throughout cell division, not because of decreased FR function. Conversely, there was an inverse association with FR levels and cell growth (r = -0.998 to -0.999, P < 0.05) in cells endogenously expressing FR, with a significant increase in the percentage of total FR located in an intracellular compartment as growth slowed. These results suggest FR function is regulated by cellular requirements for folates but not in response to changing FR levels or cellular levels of this vitamin.

KEY WORDS: • humans • folate receptor • folate uptake • cell growth

This article has been cited by other articles:

				E. Nakano, F. A. Taiwo, D. Nugent, H. R. Griffiths, S. Aldred, M. Paisi, M. Kwok, P. Bhatt, M. H. E. Hill, S. Moat, et al. Downstream effects on human low density lipoprotein of homocysteine exported from endothelial cells in an in vitro system J. Lipid Res., March 1, 2005; 46(3): 484 - 493. [Abstract] [Full Text] [PDF]

				M. M. Doucette and V. L. Stevens Point Mutations Alter the Cellular Distribution of the Human Folate Receptor in Cultured Chinese Hamster Ovary Cells J. Nutr., February 1, 2004; 134(2): 308 - 316. [Abstract] [Full Text] [PDF]

				X. Wang and M. Fenech A comparison of folic acid and 5-methyltetrahydrofolate for prevention of DNA damage and cell death in human lymphocytes in vitro Mutagenesis, January 1, 2003; 18(1): 81 - 86. [Abstract] [Full Text] [PDF]