Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer.
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.
Yiangou
C
C
Department of Medical Oncology, Charing Cross and Westminster Medical School, London, UK.
Cox
H
H
Bansal
G S
GS
Coope
R
R
Gomm
J J
JJ
Barnard
R
R
Walters
J
J
Groome
N
N
Shousha
S
S
Coombes
R C
RC
Johnston
C L
CL
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
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