Clinical Cancer Research, Vol 2, Issue 7 1135-1141, Copyright © 1996 by American Association for Cancer Research

ARTICLES

Characterization of folate receptor from normal and neoplastic murine tissue: influence of dietary folate on folate receptor expression

SB Gates, LG Mendelsohn, KA Shackelford, LL Habeck, JD Kursar, LS Gossett, JF Worzalla, C Shih and GB Grindey
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.

Membrane-associated folate receptors (FRs) have been detected in many mammalian species, and multiple isoforms have been identified. The pharmacological properties of FRs from murine kidney, liver, and six murine tumors were characterized. Murine kidney expressed primarily folate-binding protein 1, analogous to human FR-alpha, whereas murine liver expressed predominantly folate-binding protein 2, analogous to human FR-beta. Five of six murine tumors expressed high-affinity FRs with pharmacological properties consistent with folate-binding protein 1 isoform expression. Restriction of dietary folate resulted in significant changes in the FR expression in most murine tissues. Kidney and tumor FRs showed a decreased affinity for folic acid, suggesting a change in isoform expression in response to a low folate diet. Density of the FR in the kidney decreased, and, in contrast, density of the FR in all tumors increased. The response of the liver to a low folate diet was unique in that there were no detectable changes in affinity or density of liver FR. Changes in dietary folate that modulate FR isoform expression may have relevance for cancer patients treated with antifolates.

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