Taken together, these results demonstrated that the peptide FP16, acting as an FGF3 antagonist, is a promising therapeutic agent for the treatment of breast cancer.
Therefore, in this study, locus 11q13 and FGF3 gene (11q13) function were investigated in a radiation and estrogen breast cancer model induced by high-LET (α-particle) radiation and estrogen exposure.
When qPCR-identified amplifications in FGFR1, FGFR2, or FGF3 were grouped to define an FGF pathway-amplified breast cancer in HR-positive patients, the mean reduction in target lesions was 21.1% compared with a 12.0% increase in patients who did not present with FGF pathway-amplified breast cancer.
Discovery of 3-(2,6-dichloro-3,5-dimethoxy-phenyl)-1-{6-[4-(4-ethyl-piperazin-1-yl)-phenylamino]-pyrimidin-4-yl}-1-methyl-urea (NVP-BGJ398), a potent and selective inhibitor of the fibroblast growth factor receptor family of receptor tyrosine kinase.
The CCND1-FGF19-FGF4-FGF3 gene cluster in human chromosome 11q13 is amplified in breast cancer, squamous cell carcinoma of head and neck, and bladder tumors, and is also translocated in parathyroid tumors and B-cell lymphoma.
Infrequent (< or =12%) or absent LOH was detected at the remaining loci, including several loci commonly mutated in breast cancer (i.e., INT2, PYGM, and NM23).
A rapid, non-radioactive approach based on qdPCR and fluorescent DNA technique was applied for determination of int-2 and c-erbB2 gene amplification and correlated with other prognostic factors in 70 breast cancer samples.
Other members of the fibroblast growth factor family have been either not expressed in the human breast (FGF3, FGF4) or have been found at much reduced levels in breast cancer (FGF1, FGF2) and this is the first member of the family to potentially influence the progression of breast cancer through stimulation of cell division.
The role of int-2 oncogene amplification on the prognosis of breast cancer patients was investigated in 128 patients with node-negative primary breast cancers given first-line local-regional treatments until relapse and with a median follow-up of 65 months.
After a median follow-up period of 66 months, CCND1 or INT-2 amplification was not associated with significant increases in relapse or death from breast cancer.
To attain this goal, amplification of different oncogenes (HER-2/neu, c-MYC and INT-2) was studied in primary tumors of a series of 259 patients with breast cancer (median follow-up of 72 mo).
Breast cancer: prognostic significance of c-erb-B2 and int-2 amplification compared with DNA ploidy, S-phase fraction, and conventional clinicopathological features.
This is the first report of an association between amplification of the int-2 oncogene in breast tumours and a significantly increased risk of death from breast cancer, and suggests that int-2 may be useful for identifying breast-cancer patients having a poor prognosis.
We conclude that, compared to amplification of HER2/NEU, MYC, or INT2 oncogene loci, p53 gene mutations and deletions are the most frequently observed genetic change in breast cancer related to a single gene.
Patients with INT2/HST1 amplified breast cancer had a significantly shorter disease-free survival compared to those with unamplified genes (P = 0.015, median follow up 45 months).
Some of these mutations involve amplification of protooncogenes (c-myc, c-erbB-2, and int-2) that have been shown to contribute to experimentally induced breast cancer in mouse model systems.
Five proto-oncogenes were found to be occasionally amplified in primary breast cancers: c-ERBB-2 (11%), c-MYB (3%), c-RAS-Ki (3%), INT-2 (4%) and c-MYC (6%).
These findings confirm and extend earlier results of studies of int-2, c-erbB-2 and c-myc amplification in human breast cancers and point to a role for int-2 activation in certain cases of recurrent breast malignant neoplasia.
The human int-2 locus was found to be amplified 7- to 25-fold in 4 of 46 infiltrating ductal breast cancers and 30- to 60-fold in 2 of 8 squamous carcinomas of the head and neck region, but not in other cancers.