The half-life of the transcript encoding the folate receptor α in KB cells is reduced by cytosolic proteins expressed in folate-replete and not in folate-depleted cells

Sadasivan, Easwara; Regec, Annette L.; Rothenberg, Sheldon P.

doi:10.1016/s0378-1119(02)00591-7

Cited by 19 publications

(17 citation statements)

References 27 publications

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“…The short-term negative impact of this procedure upon total Folr1 expression supports the finding of Saitsu et al (2003) and Sato et al (2008), where the site of neural tube closure/neural crest formation also is a principal site of Folr1 expression in the early (2-10 somite) embryo. The apparent rebound effect of the Folr1 expression that occurred between 48 and 96 hr subsequent its initial knockdown is consistent with the magnitude of Folr1 up-regulation that can occur within 8 hr of the onset of a folate deficiency in several cell lines or in kidney cells (Hsueh and Dolnick, 1993;Said et al, 2000;Zhu et al, 2001;Sadasivan et al, 2002;Antony et al, 2004). Additionally, the expression of the folate receptor can be induced during folate insufficiency in some tissues where it is not normally expressed (Xiao et al, 2005).…”

Section: Discussionsupporting

confidence: 55%

“…Additionally, the expression of the folate receptor can be induced during folate insufficiency in some tissues where it is not normally expressed (Xiao et al, 2005). The increases in expression of this gene are thought to be due to both an increase in transcription rate and an increase in its RNA stability (Sadasivan, et al, 2002). Therefore, it is possible that there is a compensatory overexpression of Folr1 expression consequent to siRNA knockdown.…”

Section: Discussionmentioning

confidence: 99%

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High‐affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

Rosenquist

Chaudoin

Finnell

et al. 2010

Developmental Dynamics

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Folate supplementation reduces the incidence of congenital heart defects, but the nature of this protective mechanism remains unclear. Immunolabeling demonstrated that the neural tube and neural crest (NC) cells were rich in the high-affinity folate receptor FOLR1and during the early stages of development FOLR1 was found principally in these cells. Suppression of Folr1 expression in the nascent cardiac NC by site-directed short-interfering RNA (siRNA) altered cardiac NC cell mitosis and subsequent migration patterns leading to abnormal development of the pharyngeal arch arteries (PAA) and outflow tract. qPCR analysis demonstrated that the siRNA treatment significantly reduced Folr1 24 hr after treatment. These treatments also significantly reduced mitosis in the neural tube, but adjacent, nontreated areas were unaffected. In summary, a brief reduction in the expression of Folr1 during a critical stage of NC development had long-term consequences for the development of the PAA and outflow tract. Developmental Dynamics 239:1136-1144,

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Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

High‐affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

Rosenquist

Chaudoin

Finnell

et al. 2010

Developmental Dynamics

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“…This adaptive mechanism has previously been shown to be mediated by an increase in transcription rate and transcript half-life [33,36]. It is noteworthy that in NCM460 cells, FOLR1 expression and cell proliferation are similar for the upper three folate concentrations and then significantly increase and decrease at 25 nM folate, respectively.…”

Section: Discussionmentioning

confidence: 71%

“…Previous studies have shown that Folate Receptor 1 (FOLR1) [33][34][35][36] is up-regulated due to folate depletion in vitro, while it is the reduced folate carrier (RFC) that is upregulated in the rat intestine [37,38], with the FOLR1 remaining undetectable [38]. Increased FOLR1 in vitro and the increased RFC in vivo reflect the abundance of available forms in the particular model and the affinity of each protein for them.…”

Section: Introductionmentioning

confidence: 99%

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

Crott

Liu

Keyes

et al. 2008

The Journal of Nutritional Biochemistry

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Folate deficiency may affect gene expression by disrupting DNA methylation patterns or by inducing base substitution, DNA breaks, gene deletions and gene amplification. Changes in expression may explain the inverse relationship observed between folate status and risk of colorectal cancer. Three cell lines derived from the normal human colon, HCEC, NCM356 and NCM460, were grown for 32-34 days in media containing 25, 50, 75 or 150 nM folic acid, and the expression of genes involved in cell-cycle checkpoints, intracellular signaling, folate uptake and cell adhesion and migration was determined. Expression of Folate Receptor 1 was increased with decreasing media folate in all cell lines, as was p53, p21, p16 and β-catenin. With decreasing folate, the expression of both E-cadherin and SMAD-4 was decreased in NCM356. APC was elevated in NCM356 but unchanged in the other lines. No changes in global methylation were detected. A significant increase in p53 exon 7-8 strand breaks was observed with decreasing folate in NCM460 cells. The changes observed are consistent with DNA damage-induced activation of cell-cycle checkpoints and cellular adaptation to folate depletion. Folate-depletion-induced changes in the Wnt/APC pathway as well as in genes involved in cell adhesion, migration and invasion may underlie observed relationships between folate status and cancer risk.

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“…However, others observed that the interaction of various proteins within this region transcriptionally increased P1 promoter activity 76 or inhibited FOLR1 gene expression 73 in ovarian carcinoma. Sadasivan et al 77 showed that elevated FRa was mediated by both a 4.5-fold increase in the initial transcription rate of KB cells and a 2.4-fold prolongation of FOLR1 mRNA half-life following transfer from a folic acid-replete to a folate-deplete culture medium. An RNA gel-shift assay of the FOLR1 5 0 UTR and a portion of the 3 0 coding region revealed unique complexes with cytosolic proteins from KB cells grown in folic acid-replete cultures that were not observed with the cytosol from KB cells grown in folatedeplete cultures.…”

Section: Other Reports Of Transcriptional and Translational Regulationmentioning

confidence: 99%

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

Kelemen

2006

Intl Journal of Cancer

438

340

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Folate receptor a (FRa) is a membrane-bound protein with high affinity for binding and transporting physiologic levels of folate into cells. Folate is a basic component of cell metabolism and DNA synthesis and repair, and rapidly dividing cancer cells have an increased requirement for folate to maintain DNA synthesis, an observation supported by the widespread use of antifolates in cancer chemotherapy. FRa levels are high in specific malignant tumors of epithelial origin compared to normal cells, and are positively associated with tumor stage and grade, raising questions of its role in tumor etiology and progression. It has been suggested that FRa might confer a growth advantage to the tumor by modulating folate uptake from serum or by generating regulatory signals. Indeed, cell culture studies show that expression of the FRa gene, FOLR1, is regulated by extracellular folate depletion, increased homocysteine accumulation, steroid hormone concentrations, interaction with specific transcription factors and cytosolic proteins, and possibly genetic mutations. Whether FRa in tumors decreases in vivo among individuals who are folate sufficient, or whether the tumor's machinery sustains FRa levels to meet the increased folate demands of the tumor, has not been studied. Consequently, the significance of carrying a FRa-positive tumor in the era of folic acid fortification and widespread vitamin supplement use in countries such as Canada and the United States is unknown. Epidemiologic and clinical studies using human tumor specimens are lacking and increasingly needed to understand the role of environmental and genetic influences on FOLR1 expression in tumor etiology and progression. This review summarizes the literature on the complex nature of FOLR1 gene regulation and expression, and suggests future research directions. ' 2006 Wiley-Liss, Inc.

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The half-life of the transcript encoding the folate receptor α in KB cells is reduced by cytosolic proteins expressed in folate-replete and not in folate-depleted cells

Cited by 19 publications

References 27 publications

High‐affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

High‐affinity folate receptor in cardiac neural crest migration: A gene knockdown model using siRNA

Moderate folate depletion modulates the expression of selected genes involved in cell cycle, intracellular signaling and folate uptake in human colonic epithelial cell lines

The role of folate receptor α in cancer development, progression and treatment: Cause, consequence or innocent bystander?

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