Folate Receptors in Malignant and Benign Tissues of Human Female Genital Tract

作者: Jan Holm , Steen Ingemann Hansen , Mimi Høier-Madsen , Poul Erik Helkjær , Carl W. Nichols

DOI: 10.1023/A:1027313502270

关键词: Folic acid bindingBiochemistryUterusImmunostainingBiologyFolate-binding proteinFolate receptorReceptorCooperative bindingAntibodyBiophysicsCell biologyMolecular biology

摘要: We have characterized the folate receptor in malignant and benign tissues of human female genital tract (Fallopian tube and benign and malignant tissues of uterus). Radioligand binding displayed characteristics similar to those of other folate binding proteins. Those include a high-affinity type of binding (K=1010M−1), apparent positive cooperativity, a slow dissociation at pH 7.4 becoming rapid at pH 3.5, and inhibition of binding by folate analogues. The gel filtration profile of Triton X-100 solubilized tissue contained two large peaks of 3H-folate labelled protein (>=130 and 100kDa) as well as a 25 kDa peak. Only a single band of 70 kDa was seen on SDS-PAGE immunoblotting. The large molecular size forms on gel filtration appear to represent folate receptors having a hydrophobic membrane anchor inserted into Triton X-100 micelles. The folate receptor of female genital tract showed cross-reactivity in ELISA and positive immunostaining with rabbit antibodies against human milk folate binding protein. Variations in the ratio of immunoresponse to total high affinity folic acid binding suggests the presence of multiple isoforms of the receptor in different types of malignant and benign tissues.

参考文章(25)
Maria I. Colnaghi, Verna Frasca, Leslie R. Coney, Barton A. Kamen, Antonella Tomassetti, Vincent R. Zurawski, Leon Carayannopoulos, Cloning of a tumor-associated antigen: MOv18 and MOv19 antibodies recognize a folate-binding protein. Cancer Research. ,vol. 51, pp. 6125- 6132 ,(1991)
E Sadasivan, S P Rothenberg, The complete amino acid sequence of a human folate binding protein from KB cells determined from the cDNA. Journal of Biological Chemistry. ,vol. 264, pp. 5806- 5811 ,(1989) , 10.1016/S0021-9258(18)83621-3
P C Elwood, M A Kane, R M Portillo, J F Kolhouse, The isolation, characterization, and comparison of the membrane-associated and soluble folate-binding proteins from human KB cells. Journal of Biological Chemistry. ,vol. 261, pp. 15416- 15423 ,(1986) , 10.1016/S0021-9258(18)66727-4
Tania A. Jones, William D. Foulkes, Ian G. Campbell, John Trowsdale, Folate-binding Protein Is a Marker for Ovarian Cancer Cancer Research. ,vol. 51, pp. 5329- 5338 ,(1991)
Nancy Potischman, Louise A. Brinton, Rosa C. de Britton, Rolando Herrero, Maria M. Brenes, Francisco Tenorio, William C. Reeves, Eduardo Gaitan, Virginia A. Laiming, A Case-Control Study of Serum Folate Levels and Invasive Cervical Cancer Cancer Research. ,vol. 51, pp. 4785- 4789 ,(1991)
C E Butterworth, K D Hatch, H Gore, H Mueller, C L Krumdieck, Improvement in cervical dysplasia associated with folic acid therapy in users of oral contraceptives. The American Journal of Clinical Nutrition. ,vol. 35, pp. 73- 82 ,(1982) , 10.1093/AJCN/35.1.73
N C Kaarsholm, A M Kolstrup, S E Danielsen, J Holm, S I Hansen, Ligand-induced conformation change in folate-binding protein. Biochemical Journal. ,vol. 292, pp. 921- 925 ,(1993) , 10.1042/BJ2920921
R. Anderson, B. Kamen, K. Rothberg, S. Lacey, Potocytosis: sequestration and transport of small molecules by caveolae Science. ,vol. 255, pp. 410- 411 ,(1992) , 10.1126/SCIENCE.1310359