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.
Amplification and expression of these genes is particularly interesting in the context of oncovirus involvement, because INT2 is a homolog of mouse int2 which causes mammary carcinoma in mice when activated by integration of retrovirus mouse mammary tumor virus.
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.
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).
Genetic alterations have been described in breast carcinomas under the headings of loss of heterozygosity (1p, 3p, 7q, 11p, 17p, 17 and 18q), mutations (p53, c-H-ras-1), and/or gene amplifications (c-myc, int-2/FGF3, and c-erbB-2/neu).
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.
The glutathione S-transferase gene (GST pi) is located on the same chromosome band (11q13) as proto-oncogenes INT2 and HSTF1 which are frequently amplified in breast cancer.
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).