Expression of <i>fgf</i> and <i>fgf</i> receptor genes in human breast cancer

Penault‐Llorca, Frédérique; Bertucci, François; Adélaı̈de, José; Parc, Patricia; Coulier, François; Jacquemier, Jocelyne; Birnbaum, Daniel; deLapeyrière, Odile

doi:10.1002/ijc.2910610205

Cited by 213 publications

(163 citation statements)

References 17 publications

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“…It has previously been shown that the predominant form of FGFR-1 mRNA transcribed is the 5-form with the a-form present as a minority species (Luqmani et al, 1995;Penault-Llorca et al, 1995). Our results show that this is also the case for the receptor proteins.…”

Section: Discussionsupporting

confidence: 78%

“…Our results show that the FGFR-1 mRNA previously described in breast cell lines and human breast cancers (Lehtola et al, 1992;Luqmani et al, 1992;Luqmani et al, 1995;Penault-Llorca et al, 1995) does get translated into protein. It has previously been shown that the predominant form of FGFR-1 mRNA transcribed is the 5-form with the a-form present as a minority species (Luqmani et al, 1995;Penault-Llorca et al, 1995).…”

Section: Discussionsupporting

confidence: 66%

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Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer

Yiangou

Cox²,

Bansal³

et al. 1997

Br J Cancer

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Summary Monoclonal antibodies against two epitopes of FGFR-1 have been used to investigate FGFR-1 expression in the normal and neoplastic human breast. Different forms are detected in the different cell types constituting 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 form of FGFR-1, whereas the 106-kDa band is truncated at the carboxyl terminus. The 106-kDa form of FGFR-1 is the major form present in breast fibroblasts and myoepithelial cells, whereas epithelial cells contain equal amounts of the 11 5-kDa and 106-kDa forms. Breast cancer cells, however, appear to contain only the 115-kDa form of FGFR-1. This expression pattern is reflected in malignant and non-malignant tissue samples. Using reverse transcription polymerase chain reaction (RT-PCR) analysis, we have shown that the 1 06-kDa FGFR-1 isoform is not the previously described alpha 2 receptor that arises from a 25-base pair insertion in the second kinase domain. It is probable that the 106-kDa FGFR-1 has different signalling properties to the full-length receptor, having lost at least one tyrosine at amino acid 766, which is required for 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.Keywords: fibroblast growth factor receptor 1; splice variant; human breast cancer; epithelial/myoepithelial cell; monoclonal antibodyThe family of fibroblast growth factors comprises nine structurally related polypeptides that are mitogenic for a variety of cells and that are involved in embryogenesis, angiogenesis and differentiation (Burgess and Maciag, 1989;Miyamoto et al, 1993). Their cellular response is thought to be mediated through cell surface receptors that belong to the superfamily of tyrosine kinase receptors (Johnson et al, 1991;Keegan et al, 1991;Partanen et al, 1991;Jaye et al, 1992). Extracellular matrix and cell surface heparan sulphate proteoglycans are involved in the interaction of these growth factors with their receptors (Klagsbrun and Baird, 1991;Kan et al, 1993).The four fibroblast growth factor receptors are type four tyrosine kinase receptors and are encoded by four distinct genes. They consist of an extracellular ligand binding domain, a transmembrane part and an intracellular split kinase domain that is involved in signal transduction (Figure lA). They share a high amino acid sequence homology and are characterized by a large number of variant forms generated by alternative mRNA splicing (Hou et al, 1991;Jaye et al, 1992). Variants include: the full-length alpha form; the beta form lacking the first immunoglobulin domain; the intracellular gamma form lacking a signal peptide, the first immunoglobulin domain and the acidic box; and a truncated form, alpha 2, which results from a 25-bp insertion in the second kinase domain leading to a frame shift ( Figure IB). The precise biological func...

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Section: Discussionsupporting

confidence: 78%

Section: Discussionsupporting

confidence: 66%

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer

Yiangou

Cox²,

Bansal³

et al. 1997

Br J Cancer

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“…Indeed, the FGFR-1, FGFR-2 andFGFR-3 genes are amplified in 12.7%, 11.5% and 10% of breast cancers, respectively; they are also expressed at high levels in, respectively, 22%, 4% and 32% of the breast tumor samples [14,15]. Messenger RNAs for fgf-1, fgf-2 are present in all samples of breast cancer; whereas mRNA for fgf-5, fgf-6, fgf-7, fgf-8 and fgf-9 are detectable in various percentages of the tumor samples [14,15]. The production of FGF-1 and FGF-2 is down-regulated in the tumoral cells in comparison with normal tissue or begnin tumors [16,17].…”

Section: Introductionmentioning

confidence: 99%

“…MCF7 breast cancer cells were chosen, since their low tumorigenicity and the presence of estrogen and progesterone receptors [23] are interesting properties to study the progression of breast cancer cells in particular from hormonedependence to hormone-independence [24,25]. The messenger RNA for the four FGF receptor genes are detected in MCF7 cells [14,26]. Thus, it was demonstrated that MCF7 cells that overexpress FGF-1 become tumorigenic and metastatic in mice not supplemented with estrogen [27,28].…”

Section: Introductionmentioning

confidence: 99%

Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4

Hajitou

Deroanne

Noël

et al. 2000

Breast Cancer Res Treat

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SummaryThe transforming properties of fibroblast growth factor 3 (FGF-3) were investigated in MCF7 breast cancer cells and compared to those of FGF-4, a known oncogenic product. The short form of fgf-3 and the fgf-4 sequences were each introduced with retroviral vectors and the proteins were only detected in the cytoplasm of the infected cells, as expected. In vitro, cells producing FGF-3 (MCF7.fgf-3) and FGF-4 (MCF7.fgf-4) displayed an amount of estrogen receptors decreased to around 45% of the control value. However, MCF7.fgf-3 cell proliferation remained responsive to estradiol supply. The sensitivity of the MCF7.fgf-4 cells, if existant, was masked by the important mitogenic action exerted by FGF-4. In vivo, the MCF7.fgf-3 and MCF7.fgf-4 cells gave rise to tumors under conditions in which the control cells were not tumorigenic. Supplementing the mice with estrogen had the paradoxical effect of totally suppressing the start of the FGF-3 as well as the FGF-4 tumors. Tumorigenicity in the presence of matrigel was similar for MCF7.fgf-3 and control cells and was increased by estrogen supplementation. Once started, the MCF7.fgf-4 tumors grew with a characteristic high rate. Remarkably, FGF-4 but not FGF-3, stimulated the secretion of vascular endothelial growth factor (VEGF 165 ) without altering the steady-state level of its mRNA, suggesting a possible regulation of VEGF synthesis at the translational level in MCF7 cells. The increased VEGF secretion is probably involved in the more aggressive phenotype of the MCF7.fgf-4 cells while a decreased dependence upon micro-environmental factors might be part of the increased tumorigenic potential of the MCF7.fgf-3 cells.

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“…It is produced by stromal fibroblasts and acts via the KGF receptor (FGFR2-IIIb) on epithelial cells . Other studies show no expression of FGF3 and FGF4 in human breast cancers but expression of all other FGFs in at least a small proportion of breast cancers (Penault-Llorca et al, 1995). All four of the FGFRs are expressed to some degree in breast cell lines (McLeskey et al, 1994;Johnston et al, 1995).…”

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confidence: 97%

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer

et al. 2002

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Fibroblast growth factor 8 can transform NIH3T3 cells and its expression has been found to be associated with breast and prostate cancer. Following our finding that fibroblast growth factor 8 mRNA expression is increased in breast cancer, we have undertaken an immunohistochemistry study of fibroblast growth factor 8 expression in a series of human breast tissues and other normal tissues. Our findings confirm increased expression of fibroblast growth factor 8 in malignant breast tissue but also show significant fibroblast growth factor 8 expression in non-malignant breast epithelial cells. No significant difference in fibroblast growth factor 8 expression was found between different grades of ductal carcinoma, lobular carcinoma and ductal carcinoma in-situ or cancer of different oestrogen receptor, progesterone receptor or nodal status. The highest levels of fibroblast growth factor 8 expression were found in lactating breast tissues and fibroblast growth factor 8 was also detected in human milk. A survey of other normal tissues showed that fibroblast growth factor 8 is expressed in the proliferative cells of the dermis and epithelial cells in colon, ovary fallopian tube and uterus. Fibroblast growth factor 8 appears to be expressed in several organs in man and appears to have an importance in lactation.

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Expression of fgf and fgf receptor genes in human breast cancer

Cited by 213 publications

References 17 publications

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer

Down-regulation of a novel form of fibroblast growth factor receptor 1 in human breast cancer

Progression in MCF-7 breast cancer cell tumorigenicity: compared effect of FGF-3 and FGF-4

Fibroblast growth factor 8 is expressed at higher levels in lactating human breast and in breast cancer

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