Differential Roles of Fibroblast Growth Factor Receptors (FGFR) 1, 2 and 3 in the Regulation of S115 Breast Cancer Cell Growth

Tarkkonen, Kati; Nilsson, Elise; Kähkönen, Tiina E.; Dey, Julien H.; Heikkilä, Jari; Tuomela, Johanna; Liu, Qing; Hynes, Nancy E.; Härkönen, Pirkko

doi:10.1371/journal.pone.0049970

Cited by 25 publications

(16 citation statements)

References 48 publications

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“…Interestingly, upregulation of the mRNA for Fgfr1c and downregulation of the mRNA for Fgfr2c were found in the prostates of FGF8b-Tg and FGF8b-Tg-BERKO FVB mice. This observation is consistent with our previous results in S115 mouse mammary tumor cells, MCF7 breast cancer cells (Ruohola et al 1995, Tarkkonen et al 2012, and the epididymides of FGF8b-Tg mice (Elo et al 2012), indicating that FGF signaling regulates the expression of FGFRs. Results described in a previous report have demonstrated that FGF8 upregulates the expression of Fgfr1 in the neuronal cells (Mott et al 2010).…”

Section: Discussionsupporting

confidence: 93%

Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Elo¹,

Yu²,

Valve³

et al. 2014

Endocrine-Related Cancer

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Estrogens contribute to the development and growth of the prostate and are implicated in prostate tumorigenesis. In their target tissues, estrogens mediate their effects via estrogen receptor a (ERa (ESR1)) and b (ERb (ESR2)). Hyperplasia and decreased differentiation of epithelial cells in the prostate have been reported in ERb knockout (BERKO) mice. Herein, we studied the effect of ERb deficiency on prostate tumorigenesis by crossing BERKO FVB mice with prostate-targeted human fibroblast growth factor 8b transgenic (FGF8b-Tg) mice. Consistent with results described in our previous report, the prostates of 1-year-old FGF8b-Tg mice displayed stromal aberrations, prostatic intraepithelial neoplasia (mPIN) lesions, inflammation, and occasionally cancer. The prostates of BERKO FVB mice exhibited mild epithelial hypercellularity and inflammation. The prostate phenotypes of FGF8b-Tg-BERKO FVB mice closely resembled those of FGF8b-Tg mice. However, mucinous metaplasia, indicated by Goblet-like cells in the epithelium, was significantly more frequent in the prostates of FGF8b-Tg-BERKO FVB mice when compared with FGF8b-Tg mice. Furthermore, compared with FGF8b-Tg mice, there was a tendency for increased frequency of inflammation but milder hyperplasias in the prostate stroma of FGF8b-Tg-BERKO FVB mice. The expression levels of mRNAs for FGF8b-regulated genes including osteopontin (Spp1), connective tissue growth factor (Ctgf), fibroblast growth factor receptors (Fgfrs), and steroid hormone receptors and cytokines were similar in the prostates of FGF8b-Tg and FGF8b-Tg-BERKO FVB mice. Our results indicate that ERb plays a role in the differentiation of the prostatic epithelium and, potentially, in the defensive mechanism required for protection against inflammation but do not support a direct tumor-suppressive function of ERb in the prostate of FGF8b-Tg mice. Key Words" estrogen receptor beta " fibroblast growth factor 8b " transgenic mouse " prostate " tumorigenesis

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Section: Discussionsupporting

confidence: 93%

Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Elo¹,

Yu²,

Valve³

et al. 2014

Endocrine-Related Cancer

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“…Genomewide association studies have highlighted the role of single nucleotide polymorphisms in non-hereditary breast cancer susceptibility (Marian et al, 2011). As a result, fibroblast growth factor receptor 2 (FGFR2), a gene involved in mammary gland development, has been recognized as a prominent candidate in sporadic breast cancer (Sun et al, 2010;Tarkkonen et al, 2012). FGFR2 codes a transmembrane-type receptor involved in cellular functions .…”

Section: Introductionmentioning

confidence: 99%

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Saadatian¹,

Gharesouran²,

Ghojazadeh³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Breast cancer is the most common cancer among women in the world. In Iran, the incidence of breast cancer is on the increase. We here studied the association of rs1219648 in FGFR2 and rs1042522 in TP53 and their interaction in development of early onset sporadic breast cancer in Iranian Azeri population to evaluate epistatic effects on the risk of mammary neoplasia. We genotyped the two polymorphisms in 100 women with early onset breast cancer and 100 healthy women by PCR-RFLP. Allele frequency differences were tested using chi 2 -test with 95% confident intervals. Our results indicated a statistically significant association (p<0.05) between rs1219648, but not rs1042522, and risk of breast cancer. We also found that the combination of FGFR2 major genotype and TP53 hetero genotype had protective effects against breast cancer , while the hetero allele of FGFR2 in combination with the minor genotype of TP53 was associated with a high risk. This study revealed an important crosstalk between two polymorphisms in FGFR2 and TP53 in development of breast cancer. These candidates risk variants should be further evaluated in studies with a larger sample size.

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“…Although, activating mutation and overexpression of FGFR3 is a common phenomenon observed in low-grade bladder cancer [19] , a switch from its epithelial to mesenchymal isoform with wider ligand affinity is thought to have more deleterious effects [19,26] . Particularly, Q2: Please confirm the running head FGFR1 has been considered as a potential oncogene in breast cancer because its deregulated signaling contributes to cell proliferation, growth, angiogenesis, EMT, and cell migration in S115 breast cancer [20] . Overall, FGFRs stands as an attractive target for therapeutic intervention in cancer [19,21,27] .…”

Section: Fibroblast Growth Factor Receptor (Fgfr) Familymentioning

confidence: 99%

Signaling pathways influencing tumor microenvironment and their exploitation for targeted drug delivery

Sheeba¹,

Marslin²,

Revina³

et al. 2016

Nano Online

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In the recent years, the "tumor microenvironment" has been receiving growing attention due to its involvement in neoplastic transformation, tumor growth, invasion, and protection of tumor cells from host immune response. All these events are facilitated by chemical signals produced by the tumor as well as the surrounding stromal cells.This review is divided into two main parts in which the first part discusses the receptor tyrosine kinase (RTK)-mediated growth factor signaling, steroid hormone (SH) signaling, ancient signaling pathways, and other molecules that are involved in tumorigenesis and how they interact with each other to create a complex tumor microenvironment. In the second part, we bring together the recent nanocarrier-mediated drug delivery approaches to target the signaling pathways/molecules present in the tumor microenvironment.Keywords: active targeting; functionalization; nanoparticle-mediated drug delivery; signaling pathways; tumor microenvironment Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.

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Differential Roles of Fibroblast Growth Factor Receptors (FGFR) 1, 2 and 3 in the Regulation of S115 Breast Cancer Cell Growth

Cited by 25 publications

References 48 publications

Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Deficiency of ERβ and prostate tumorigenesis in FGF8b transgenic mice

Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population

Signaling pathways influencing tumor microenvironment and their exploitation for targeted drug delivery

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