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 brea st, Different forms are detected in the different cell types constitut ing 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 f orm of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl t erminus. The 106-kDa form of FGFR-1 is the major form present in breas t fibroblasts and myoepithelial cells, whereas epithelial cells contai n 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 expr ession pattern is reflected in malignant and non-malignant tissue samp les. Using reverse transcription polymerase chain reaction (RT-PCR) an alysis, we have shown that the 106-kDa FGFR-1 isoform is not the previ ously described alpha 2 receptor that arises from a 25-base pair inser tion in the second kinase domain. It is probable that the 106-kDa FGFR -1 has different signalling properties to the full-length receptor, ha ving lost at least one tyrosine at amino acid 766, which is required f or 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.