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          Institute: MPI für Biochemie     Collection: Molecular Biology (A. Ullrich)     Display Documents

ID: 39032.0, MPI für Biochemie / Molecular Biology (A. Ullrich)
Cancer progression and tumor cell motility are associated with the FGFR4 Arg(388) allele
Authors:Bange, J.; Prechtl, D.; Cheburkin, Y.; Specht, K.; Harbeck, N.; Schmitt, M.; Knyazeva, T.; Müller, S.; Gärtner, S.; Sures, I.; Wang, H. Y.; Imyanitov, E.; Haring, H. U.; Knayzev, P.; Iacobelli, S.; Hofler, H.; Ullrich, A.
Date of Publication (YYYY-MM-DD):2002-02-01
Title of Journal:Cancer Research
Journal Abbrev.:Cancer Res.
Issue / Number:3
Start Page:840
End Page:847
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Expression analysis of genes encoding components of the phosphotyrosine signaling system by cDNA array hybridization revealed elevated levels of FGFR4 transcripts in several mammary carcinoma cell lines. In the FGFR4 gene transcript from MDA-MB-453 mammary carcinoma cells, a G to A conversion was discovered that results in the substitution of glycine by arginine at position 388 in the transmembrane domain of the receptor. The Arg(388) allele was also found in cell lines derived from a variety of other tumor types as well as in the germ-line of cancer patients and healthy individuals. Analysis of three geographically separated groups indicated that it occurs in approximately 50% of the human population. Investigation of the clinical data of 84 breast cancer patients revealed that homo- or heterozygous carriers of the Arg(338). allele had a significantly reduced disease-free survival time (P = 0.01) within a median follow-up of 62 months. Moreover, the FGFR4 Arg(338) allele was associated with early lymph node metastasis and advanced tumor-node-metastasis (TNM) stage in 82 colon cancer patients. Consistent with this finding, MDA-MB-231 mammary tumor cells expressing FGFR4 Arg(338) exhibited increased motility relative to cells expressing the FGFR4 Gly(338) isotype. Our results support the conclusion that the FGFR4 Arg(338) allele represents a determinant that is innocuous in healthy individuals but predisposes cancer patients for significantly accelerated disease progression.
Comment of the Author/Creator:Date: 2002, FEB 1
External Publication Status:published
Document Type:Article
Communicated by:N.N.
Affiliations:MPI für Biochemie/Molecular Biology (A. Ullrich)
External Affiliations:Tech Univ Munich, Dept Pathol, D-81675 Munich, Germany; Tech Univ Munich, Dept Obstet & Gynecol, D-81675 Munich, Germany; Gesell Strahlenforsch, Dept Pathol, D-85764 Neuherberg, Germany; Eastern Hepatobiliary Surg Inst, Shanghai 200438, Peoples R China; NN Petrov Oncol Res Inst, St Petersburg 189646, Russia; Univ Tubingen, Med Clin Dept 4, D-72076 Tubingen, Germany; Univ Chieti, Dept Oncol, I-66100 Chieti, Italy
Identifiers:ISI:000173740600034 [ID No:1]
ISSN:0008-5472 [ID No:2]
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