Amplification of <i>fgfr</i>4 gene in human breast and gynecological cancers

Jaakkola, Susanna; Salmikangas, P; Nylund, Stella J.; Partanen, Juha; Armstrong, Elina; Pyrhönen, Seppo; Lehtovirta, Pentti; Nevanlinna, Heli

doi:10.1002/ijc.2910540305

Cited by 142 publications

(93 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…High expression of FGFR4 has been described already for breast cancer (Lehtola et al, 1992;Jaakkola et al, 1993), pancreatic cancer (Leung et al, 1994) and renal cell carcinoma (Takahashi et al, 1999). The cytoplasmic staining of the FGFR4 in melanoma cells is in agreement with other publications investigating the expression for FGFR4 in other types of cancer (Gowardhan et al, 2005;Mawrin et al, 2005).…”

Section: Discussionsupporting

confidence: 90%

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

et al. 2006

View full text Add to dashboard Cite

A single nucleotide polymorphism in the gene for FGFR4 (ÀArg388) has been associated with progression in various types of human cancer. Although fibroblast growth factors (FGFs) belong to the most important growth factors in melanoma, expression of FGF receptor subtype 4 has not been investigated yet. In this study, the protein expression of this receptor was analysed in 137 melanoma tissues of different progression stages by immunohistochemistry. FGFR4 protein was expressed in 45% of the specimens and correlated with pTNM tumour stages (UICC, P ¼ 0.023 and AJCC, P ¼ 0.046), presence of microulceration (P ¼ 0.009), tumour vascularity (P ¼ 0.001), metastases (P ¼ 0.025), number of primary tumours (P ¼ 0.022), overall survival (P ¼ 0.047) and disease-free survival (P ¼ 0.024). Furthermore, FGFR4 Arg388 polymorphism was analysed in 185 melanoma patients by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The Arg388 allele was detected in 45% of the melanoma patients and was significantly associated with tumour thickness (by Clark's level of invasion (P ¼ 0.004) and by Breslow in mm (P ¼ 0.02)) and the tumour subtype nodular melanoma (P ¼ 0.002). However, there was no correlation of the FGFR4 Arg388 allele with overall and disease-free survival. In conclusion, the Arg388 genotype and the protein expression of FGFR4 may be potential markers for progression of melanoma.

show abstract

Section: Discussionsupporting

confidence: 90%

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

et al. 2006

View full text Add to dashboard Cite

show abstract

“…20 FGF4 gene amplification has been reported in various human cancers. [24][25][26][27] The FGF4 gene is expressed from the early stage of embryonic development in fetal life and has essential roles in cell differentiation, morphogenesis and proliferation of a variety of organizations. 28 In human adult organs, FGF4 is highly expressed in the testis.…”

Section: Discussionmentioning

confidence: 99%

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

Yasuda

Torigoe

Mariya

et al. 2014

Laboratory Investigation

View full text Add to dashboard Cite

Cancer stem-like cells (CSCs)/cancer-initiating cells (CICs) are defined as a small population of cells within cancer that contribute to cancer initiation and progression. Cancer-associated fibroblasts (CAFs) are stromal fibroblasts surrounding tumor cells, and they have important roles in tumor growth and tumor progression. It has been suggested that stromal fibroblasts and CSCs/CICs might mutually cooperate to enhance their growth and tumorigenic capacity. In this study, we investigated the effects of fibroblasts on tumor-initiating capacity and stem-like properties of ovarian CSCs/CICs. CSCs/ CICs were isolated from the ovarian carcinoma cell line HTBoA as aldehyde dehydrogenase 1 high (ALDH1 high ) population by the ALDEFLUOR assay. Histological examination of tumor tissues derived from ALDH1 high cells revealed few fibrous stroma, whereas those derived from fibroblast-mixed ALDH1 high cells showed abundant fibrous stroma formation. In vivo tumor-initiating capacity and in vitro sphere-forming capacity of ALDH1 high cells were enhanced in the presence of fibroblasts. Gene expression analysis revealed that fibroblast-mixed ALDH1 high cells had enhanced expression of fibroblast growth factor 4 (FGF4) as well as stemness-associated genes such as SOX2 and POU5F1. Sphere-forming capacity of ALDH1 high cells was suppressed by small-interfering RNA (siRNA)-mediated knockdown of FGFR2, the receptor for FGF4 which was expressed preferentially in ALDH1 high cells. Taken together, the results indicate that interaction of fibroblasts with ovarian CSCs/CICs enhanced tumor-initiating capacity and stem-like properties through autocrine and paracrine FGF4-FGFR2 signaling.

show abstract

“…About 10% of breast cancers have been shown to contain amplified levels of the genes for FGFR1 (Adnane et al, 1991;Jacquemier et al, 1994) and FGFR4 (Jaakkola et al, 1993). Jacquemier et al (1994) also reported overexpression of FGFR1 mRNA in 14.5% of breast tumours and Penault-Llorca et al (1995) found both FGFR1 and FGFR4 mRNA to be expressed at high levels in 22% and 32% of breast cancers respectively.…”

Section: Discussionmentioning

confidence: 99%

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Coope

Browne²,

Yiangou³

et al. 1997

Br J Cancer

View full text Add to dashboard Cite

Summary Acidic fibroblast growth factor (FGF1) and two of its receptors, FGFR1 and FGFR4, were localized in cryostat sections of normal, benign and malignant human breast tissue by immunohistochemistry. Without pretreatment, FGF1 staining was mainly seen in normal epithelial cells. However, polymerase chain reaction (PCR) analysis and immunoblotting of isolated normal epithelial and myoepithelial cells showed FGF1 mRNA and protein to be present in both cell types. Following incubation of frozen sections at 370C in phosphate-buffered saline, FGF1 staining was also revealed in myoepithelial cells and basement membrane adjacent to carcinoma cells. Treatment with protease inhibitors demonstrated that this effect was due to the activity of an endogenous protease. In contrast, FGF1 staining was found to be associated with the stroma adjacent to malignant cells only in the presence of protease inhibitors. FGFR1 and FGFR4 immunostaining was localized to both normal and malignant epithelial cells and to a lesser extent to myoepithelial cells. There was no difference in the staining intensity for the FGF receptors between normal and cancer samples. The change in location of FGF1 between normal and malignant tissues and the sensitivity of stored FGF1 to the action of endogenous proteases raises the possibility of both autocrine and paracrine roles for FGF1 in the normal and malignant human breast.Keywords: breast cancer; fibroblast growth factor 1; protease; immunohistochemistry Fibroblast growth factor 1 (FGF1) belongs to a family of multifunctional polypeptides that are involved in a wide array of biological processes, which include cellular proliferation and differentiation, angiogenesis, chemotaxis, embryonal development and tissue repair (Basilico and Moscatelli, 1992). To date, the FGFs consist of a family of nine homologous polypeptide growth factors that include FGF1 (acidic FGF), FGF2 (basic FGF), FGF3 (int-2), FGF4 (hst-l/Kaposi FGF), FGF5, FGF6 (hst-2), FGF7 (keratinocyte growth factor), FGF8 (androgen-induced growth factor) and FGF9 (glial-activating factor) (Basilico and Moscatelli, 1992;Tanaka et al, 1992;Miyamoto et al, 1993). These proteins share 35-50% overall homology of their amino acid sequences (Basilico and Moscatelli, 1992;Givol and Yayon, 1992).Unlike other members of the family, FGF1, FGF2 and FGF9 are synthesized without a signal peptide sequence and thus may remain sequestered in the cell (Basilico and Moscatelli, 1992;Cao and Pettersson, 1993). However, release of FGF may occur through leakage from damaged cells or from viable cells via a novel mechanism (Mignatti et al, 1992;Cao and Pettersson, 1993). Yeoman (1993) has postulated that proteoglycan-bound FGF may be released from the cell surface or extracellular matrix by the action of proteases, and Briozzo et al (1991) have shown that Received 10 June 1996 Revised 26 November 1996 Accepted 3 December 1996 Correspondence to: J Gomm MCF7 breast cancer cells secrete cathepsin D, which is able to digest the extracellular matrix and releas...

show abstract

Amplification of fgfr4 gene in human breast and gynecological cancers

Cited by 142 publications

References 39 publications

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

FGFR4 Arg388 allele correlates with tumour thickness and FGFR4 protein expression with survival of melanoma patients

Fibroblasts induce expression of FGF4 in ovarian cancer stem-like cells/cancer-initiating cells and upregulate their tumor initiation capacity

The location of acidic fibroblast growth factor in the breast is dependent on the activity of proteases present in breast cancer tissue

Contact Info

Product

Resources

About