title: Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer.
abstract: Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting the normal breast. Moreover, breast cancer cells lack one form of FGFR-1. Western blot analysis showed 115-kDa and 106-kDa forms of FGFR-1 within the human breast. The 115-kDa band corresponds to the beta form of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl terminus. The 106-kDa form of FGFR-1 is the major form present in breast fibroblasts and myoepithelial cells, whereas epithelial cells contain equal amounts of the 115-kDa and 106-kDa forms. Breast cancer cells, however, appear to contain only the 115-kDa form of FGFR-1. This expression pattern is reflected in malignant and non-malignant tissue samples. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, we have shown that the 106-kDa FGFR-1 isoform is not the previously described alpha 2 receptor that arises from a 25-base pair insertion in the second kinase domain. It is probable that the 106-kDa FGFR-1 has different signalling properties to the full-length receptor, having lost at least one tyrosine at amino acid 766, which is required for phospholipase C activation. This form of FGFR-1 appears to be lost in all breast cancer cells analysed and its absence may have a bearing on malignancy.
authors.affiliation: Department of Medical Oncology, Charing Cross and Westminster Medical School, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Yiangou
authors.forename: H
authors.initials: H
authors.lastname: Cox
authors.forename: G S
authors.initials: GS
authors.lastname: Bansal
authors.forename: R
authors.initials: R
authors.lastname: Coope
authors.forename: J J
authors.initials: JJ
authors.lastname: Gomm
authors.forename: R
authors.initials: R
authors.lastname: Barnard
authors.forename: J
authors.initials: J
authors.lastname: Walters
authors.forename: N
authors.initials: N
authors.lastname: Groome
authors.forename: S
authors.initials: S
authors.lastname: Shousha
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
authors.forename: C L
authors.initials: CL
authors.lastname: Johnston
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001940:Breast / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D015536:Down-Regulation / Q000502:physiology; D004847:Epithelial Cells / Q000648:ultrastructure; D005347:Fibroblasts / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D007536:Isomerism; D008969:Molecular Sequence Data; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017468:Receptors, Fibroblast Growth Factor / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D012333:RNA, Messenger; D017468:Receptors, Fibroblast Growth Factor; C496348:FGFR1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1