(2) The human homolog of int-2, located on chromosome 11q13, is frequently amplified in human primary tumors and is comprised in an amplification unit encompassing the hst gene, which is often coamplified; the amplification at the 11q13 locus in breast carcinomas correlates with a poor outcome of the disease.
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.
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).
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).
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.
Breast cancer: prognostic significance of c-erb-B2 and int-2 amplification compared with DNA ploidy, S-phase fraction, and conventional clinicopathological features.
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.
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.
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.
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.
In an attempt to probe the significance of HST and INT-2 gene amplification in human breast carcinomas, we have surveyed the amplification status of five molecular markers located on the long arm of chromosome 11 (BCL-1, HST, INT-2 & SEA on 11q13, and ETS-1 on 11q23) in a population of 297 mammary tumors.
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.
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.
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 have compared the cytosolic cath-D level and the amplification of three oncogenes: c-myc, neu-erb-B-2 and int-2 in 140 primary breast carcinomas and 64 axillary lymph nodes collected in 1987 and 1988 at the Cancer Center of Montpellier (Centre Paul Lamarque).
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).
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.
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.