Increased expression of fibroblast growth factor 8 in human breast cancer

Marsh, Sharon; Bansal, G S; Zammit, Charles; Barnard, R.; Coope, R. C.; Roberts-Clarke, D; Gomm, Jennifer J.; Coombes, R. Charles; Johnston, C L

doi:10.1038/sj.onc.1202392

Cited by 75 publications

(63 citation statements)

References 49 publications

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“…Since ephithelial cells exclusively express FGFR2-IIIb and FGF7 is secreted by fibroblasts, FGF7 is likely to act in a paracrine fashion . A similar situation may occur in the case of FGF8, which is expressed principally in epithelial cells with very little expression seen in stromal tissues in this study and in other reports (Tanaka et al, 1998;Marsh et al, 1999). Its receptor binding properties have been reported previously and the highest affinity receptors are FGFR2-IIIc, FGFR3-IIIc and FGFR4 (Ornitz et al, 1996).…”

Section: Discussionsupporting

confidence: 90%

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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Section: Discussionsupporting

confidence: 90%

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

et al. 2002

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“…FGF7, which is highly homologous to FGF10, is also secreted by stromal breast cells and is a paracrine growth factor for breast epithelial cells; however, this factor was not found upregulated in breast carcinomas (Bansal et al, 1997), although expression in the epithelial component of breast cancers has been reported (Palmieri et al, 2003). Elevated expression levels of FGF8 are present in a subset of human breast cancers (Marsh et al, 1999;Tanaka et al, 2002). As both FGF8 and some of its receptors are expressed by the epithelial component of breast cancers, an autocrine activation loop may be established that could lead to tumor progression.…”

Section: Discussionmentioning

confidence: 99%

Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas

et al. 2004

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Mouse mammary tumor virus (MMTV) infection causes a high incidence of murine mammary carcinomas by insertion of its proviral DNA in the genome of mammary epithelial cells. Retroviral insertion can activate flanking proto-oncogenes by a process called insertional mutagenesis. By sequencing the DNA adjacent to MMTV proviral insertions in mammary tumors from BALB/c mice infected with C3H-MMTV, we have found a common MMTV insertion site in the Fgf10 locus. RT-PCR studies showed that Fgf10 is expressed only in those tumors harboring a MMTV proviral insertion in this locus, suggesting that Fgf10 is a proto-oncogene. The oncogenicity of Fgf10 was evaluated in vivo by subcutaneous transplantation of retrovirally transduced HC11 mammary epithelial cells into BALB/c mice. Highly vascularized invasive subcutaneous tumors developed indicating that Fgf10 can act as an oncogene. A survey of primary human breast carcinomas revealed strongly elevated Fgf10 mRNA levels in approximately 10% of the tumors tested, suggesting that Fgf10 may also be involved in oncogenicity of a subset of human breast cancers.

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“…In adult mouse, FGF-8 expression has been detected only in ovary and testis (Lorenzi et al, 1995;MacArthur et al, 1995c;Valve et al, 1997). FGF-8 is also expressed in human mammary gland and prostate but at a very low level (Ghosh et al, 1996;Tanaka et al, 1998;Marsh et al, 1999). Alternative splicing of Fgf-8 gene gives rise to potentially eight di erent protein isoforms (a ± h) in the mouse and four (a, b, e, f) in the human, di ering in the amino terminus (Crossley and Martin, 1995;MacArthur et al, 1995b;Gemel et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

“…The generation of Fgf-8 transgenic mice utilizing the MMTV promoter has been shown to produce mammary lobular adenocarcinomas, salivary gland tumors and ovarian stromal hyperplasia (Daphna-Iken et al, 1998). In addition, the expression of FGF-8 mRNA has been found in human breast cancer and in di erent human breast cancer cell lines Johnson et al, 1998;Marsh et al, 1999). FGF-8 is actually the only member of the FGF family, which is known to be expressed at an elevated level in breast cancer .…”

Section: Introductionmentioning

confidence: 99%

FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells

et al. 2001

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Fibroblast growth factor 8 (FGF-8) is a secreted heparinbinding protein, which has transforming potential. Alternative splicing of the mouse Fgf-8 gene potentially codes for eight protein isoforms (a ± h) which di er in their transforming capacity in transfected cells. S115 mouse mammary tumor cells express a transformed phenotype and secrete FGF-8 in an androgen-dependent manner. In order to study the role of FGF-8 isoforms in the induction of transformed phenotype of breast cancer cells, we over-expressed FGF-8 isoforms a, b and e in S115 cells. Over-expression of FGF-8b, but not FGF-8a or FGF-8e, induced androgen and anchorage independent growth of S115 cells. FGF-8b-transfected S115 cells formed rapidly growing tumors with increased vascularization when injected s.c. into nude mice. FGF-8a also slightly increased tumor growth and probably tumor vascularization but FGF-8e was not found to have any e ects. The angiogenic activity of FGF-8b and heparinbinding growth factor fraction (HBGF) of S115 cell conditioned media was tested in in vitro and in vivo models for angiogenesis using immortomouse brain capillary endothelial cells (IBEC) and chorion allantoic membrane (CAM) assays. Recombinant FGF-8b protein was able to stimulate proliferation, migration, and vessellike tube formation of IBECs. In addition, stimulatory e ect of S115-HBGF on IBE cell proliferation was evident. A positive angiogenic response to FGF-8b was also seen in CAM assay. The results demonstrate that the expression of Fgf-8b is able to promote vessel formation. Angiogenic capacity probably markedly contributes to the ability of FGF-8b to increase tumor growth of androgen-regulated S115 mouse breast cancer cells. Oncogene (2001) 20, 2791 ± 2804.

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Increased expression of fibroblast growth factor 8 in human breast cancer

Cited by 75 publications

References 49 publications

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

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

Fgf10 is an oncogene activated by MMTV insertional mutagenesis in mouse mammary tumors and overexpressed in a subset of human breast carcinomas

FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells

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