Markers of Fibroblast Growth Factor Family-Mediated Growth Signal Transduction asDeterminants of Successful Hormonal Therapy for Patients with Estrogen Receptor Positive Breast Cancer

摘要

Previous work from the laboratory sponsored by this award demonstrated thatoverexpression of two members of the fibroblast growth factor (FGF) family of cytokines in a estrogen-dependent human breast cancer cell line resulted in the cancer cells acquiring the ability to grow in mice that were treated with the antiestrogen tamoxifen. Other work demonstrated the presence of high levels mRNA for FGFR-3, one of the transmembrane tyrosine kinase growth factor receptors for FGFs, in a subset of human breast tumors. During the course of the period covered by this report, two high titer polyclonal rabbit antibodies were generated against two peptides present in the FGFR-3 protein. Pathological specimens from 181 patients with estrogen receptor positive breast tumors that received tamoxifen therapy were identified. The suitability of the FGFR-3 antibodies for use in immunohistochemical assays with sections from formalin-fixed and paraffin-embedded material from these patients is currently being evaluated. Reverse transcription-polymerase chain reaction (RT-PCR) was used to generate plasmid transcription vectors for FGF-7 and a FGFR-2 splice variant that generates a specific receptor for FGF-7. These vectors were used to prepare probes for RNAse protection assays for FGF-7 and its receptor. Although the probe for the receptor did not appear to be suitable for the assay, the presence of FGF-7 RNA was detected in 35 of 36 human breast tumors examined. Breast cancer, Antiestrogen resistance, Fibroblast growth factors, Growth factor.