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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We sought to determine whether the hepatocyte growth factor/scatter factor (HGF/SF)- and keratinocyte growth factor-receptor systems were expressed in normal breast cells, breast carcinoma cell lines, normal breast tissues, and breast cancer tissues. Reverse transcriptase-polymerase chain reaction and hot blotting were used to detect HGF, HGF/SF (met) receptor, KGF, and KGF receptor mRNAs in human mammary epithelial (HME) and stromal (HMS) cells. We also examined breast carcinoma (MDA-MB-157, SCC 38, and SCC 70) and spontaneously immortalized breast epithelial (HMT 3522) cell lines, as well as normal breast and breast carcinoma tissues. PCR products were also confirmed by nucleic acid sequencing. The effects of HGF and KGF, compared to EGF and heparin-binding EGF, on the proliferation of normal human mammary epithelial cells in serum-free defined medium was determined by cell counting. HGF and KGF mRNAs were detected in HMS cells, but not HME cells. KGF receptor mRNA was detected in HME cells, but not HMS cells. HGF/SF receptor mRNA was detected in both HME and HMS cells. mRNAs were also detected in normal breast and breast carcinoma tissues, as well as breast carcinoma and transformed breast epithelial cell lines. Alternative cDNA sequences that are predicted to code for a soluble KGF receptor and a membrane bound, truncated HGF/SF receptor were detected in breast epithelial cells and breast tissues. HGF and KGF maintained viability and stimulated proliferation of HME cells.
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PMID:Hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and their receptors in human breast cells and tissues: alternative receptors. 786 34

The local recurrence rate of breast cancer has been reported to be unusually high at the surgical scar. Such breast cancer recurrence is believed to be triggered by the release of growth factors into the healing wound. Observations from an animal model have also demonstrated that KGF expression is dramatically induced by creation of full thickness wounds in mouse skin. Since KGF is an epithelial cell-specific mitogen in rat mammary epithelium, it is reasonable to speculate that KGF may be also involved in regulating human breast cancer cell growth. The purpose of the present study was to determine the effect of estradiol-17 on KGF gene expression in normal human breast stromal cells, as well as in human breast cancer stromal cells, and the mechanisms by which estradiol-17 regulates breast epithelial proliferation. Our results show that KGF expression was not effected by estradiol-17 treatment in normal human breast stromal cells. In contrast, KGF expression was stimulated by estradiol-17 in human breast cancer stromal cells. KGF mRNA levels have also been examined in normal human breast stromal cells and human breast cancer stromal cells. An interesting correlation was found between KGF expression and estradiol-17 regulation in these cell types. Normal human breast stromal cells which do not response to estradiol-17 have lower KGF mRNA level than the cancer cells which KGF expression is stimulated by estradiol-17. Our data also demonstrate that recombinant human KGF significantly stimulate normal human breast and human breast cancer epithelial cell proliferation in a dose-dependent manner. Since we have shown that estradiol-17 induces KGF mRNA expression in human breast cancer stromal cells, KGF may be involved at least in part in the stimulatory pathway that is initiated by estradiol-17 in human breast cancer epithelial cells.
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PMID:Estrogen-induced keratinocyte growth factor mRNA expression in normal and cancerous human breast cells. 953 55

Estrogen is the major hormonal stimulus for growth of the hormonal-dependent type of breast cancer. The rate-limiting step in the conversion of androgens to estrogens in breast tumors is catalyzed by aromatase, one of a series of related P-450 enzymes involved in the production of steroid hormones. An interesting correlation has been found between KGF mRNA and aromatase mRNA expression in human breast tumors. Tumors that express aromatase mRNA exhibit strong KGF expression, while tumors that do not express aromatase are weak or negative for KGF expression. Thus, it is reasonable to theorize that a possible association between KGF and aromatase in controlling human breast tumor growth exists. The purpose of the current study was to establish whether there is any interaction between KGF, which is known to have epithelial-specific mitogenic activity on breast cancer cells in vitro, and the synthesis of estradiol within the hormone-dependent breast cancer epithelial cells. In the present study, we have demonstrated that KGF stimulates aromatase activity in human breast cancer cells (MCF-7) in a dose-dependent manner. Our data shows that recombinant human KGF, at a dose as low as 10 ng/ml, can significantly increase aromatase activity 2-fold over controls. In agreement with this observation, we also found that aromatase mRNA levels were increased after 10 ng/ml KGF treatment in MCF-7 cells. These results indicate that the stimulatory effect of KGF on aromatase activity may be mediated by alterations in aromatase mRNA levels or in the efficiency of the translation of the message in MCF-7 cells. In addition, our results have demonstrated that modulation of aromatase activity appears to correlate with the stimulation of proliferative activity by KGF in MCF-7 cells. These results are consistent with our previous observations that estradiol-17 beta stimulates KGF expression in human breast cancer stromal cells, leading to the speculation that breast malignant transformation is associated with a positive feedback stimulation, whereby estradiol-17 beta stimulates breast cancer stromal cell production of KGF, and KGF subsequently stimulates aromatase activity in breast cancer cells, consequently raising levels of estradiol-17 beta, in turn acts on breast stromal cells to yield more KGF. Such a positive feedback loop could play an important role in the loss of growth control in human breast cancer cells.
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PMID:Keratinocyte growth factor (KGF) induces aromatase activity in cultured MCF-7 human breast cancer cells. 970 7

Keratinocyte growth factor (FGF-7/KGF) is a secreted member of the fibroblast growth factor family, which functions primarily as an important paracrine mediator of cell growth and differentiation. Inhibitory pathways of vitamin D may also involve participation of some growth factors. To determine whether vitamin D may play a role in the expression of FGF-7, we investigated FGF-7 expression in human breast cancer cells treated with 1,25-dihydroxyvitamin D3, which inhibited the growth of the cells. By means of cDNA microarray, RT-PCR, and Western blot analysis, we have shown an increase in expression of FGF-7 on both mRNA and protein levels after vitamin D exposure. This is the first demonstration of vitamin D regulation of FGF-7 expression and its possible involvement in mediating growth and differentiation by vitamin D.
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PMID:Vitamin D induced up-regulation of keratinocyte growth factor (FGF-7/KGF) in MCF-7 human breast cancer cells. 1087 63

The fibroblast growth factor receptor (FGFR)2 gene has been shown to be amplified in 5-10% of breast cancer patients. A breast cancer cell line developed in our laboratory, SUM-52PE, was shown to have a 12-fold amplification of the FGFR2 gene, and FGFR2 message was found to be overexpressed 40-fold in SUM-52PE cells as compared with normal human mammary epithelial (HME) cells. Both human breast cancer (HBC) cell lines and HME cells expressed two FGFR2 isoforms, whereas SUM-52PE cells overexpressed those two isoforms, as well as several unique FGFR2 polypeptides. SUM-52PE cells expressed exclusively FGFR2-IIIb isoforms, which are high-affinity receptors for fibroblast growth factor (FGF)-1 and FGF-7. Differences were identified in the expression of the extracellular Ig-like domains, acid box and carboxyl termini, and several variants not previously reported were isolated from these cells.
Breast Cancer Res 2000
PMID:Characterization of fibroblast growth factor receptor 2 overexpression in the human breast cancer cell line SUM-52PE. 1105 89

In prostate cancer, a distinct series of alterations in the fibroblast growthfactor (FGF) family occurs during the progression from a hormone-dependent to independent state that disrupts communication between stroma and epithelium and results in autonomy of cancer cells. Changes include (i) loss of FGFR2IIIb, whichbinds stromal-derived FGF-7, which promotes growth, growth limitation and differentiation and (ii) activation of FGFR1, the expression of which is normally limited to stroma, along with activation of FGFs that act on FGFR1 in an autocrine manner. Transfection of the FGFR2IIIb isoform into hormone-independent prostate cancer cells not only causes growth inhibition, but also induces differentiation. However, introduction of FGFR1 by transfection in hormone-dependent prostate cancer cells accelerates their progression to malignancy. These results suggest distinct targets for therapy aimed at both inhibition of the malignant phenotype and restoration of homeostasis.
Breast Cancer 1999 Oct 25
PMID:Hormone Refractory Prostate Cancer and Fibroblast Growth Factor Receptor. 1109 37

Growth factors are known to influence the progression, motility and invasiveness of tumor cells. In a previous study, we reported that conditioned media from NIH 3T3 cells (mouse fibroblast), which contains KGF, increased the motile morphology of estrogen receptor (ER)-positive breast cancer cells and produced no effect on ER-negative cells. The present study examined the influence of human KGF on two estrogen receptor (ER)-positive human breast cancer cell lines (MCF-7 and T-47D) using a culture wounding model to evaluate cell proliferation and migration over a period of 48h. In the present study we observed that KGF enhanced the migration and proliferation of both MCF-7 and T-47D breast cancer cells. In both cell lines the response to KGF was found to be both dose- and time-dependent. However, the total migration and proliferation response of the MCF-7 cells to KGF was much greater than that observed in the T-47D cells. The results of this study demonstrate that human KGF enhances the migration and proliferation of human breast cancer cells. Further, these results support the concept that KGF may be an early signal in the progression of breast cancer to a more motile and metastatic phenotype.
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PMID:Keratinocyte growth factor stimulates the migration and proliferation of breast cancer cells in a culture wounding model. 1222 Sep 58

Bone morphogenetic proteins (BMPs) are multifunctional cytokines that elicit pleiotropic effects on biological processes such as cell proliferation, cell differentiation and tissue morphogenesis. With respect to cell proliferation, BMPs can exert either mitogenic or anti-mitogenic activities, depending on the target cells and their context. Here, we report that in low-density cultures of immortalized mammary epithelial cells, BMP-4 did not stimulate cell proliferation by itself. However, when added in combination with suboptimal concentrations of fibroblast growth factor (FGF)-2, FGF-7, FGF-10, epidermal growth factor (EGF) or hepatocyte growth factor (HGF), BMP-4 potently enhanced growth factor-induced cell proliferation. These results reveal a hitherto unsuspected interplay between BMP-4 and growth factors in the regulation of mammary epithelial cell proliferation. We suggest that the ability of BMP-4 to potentiate the mitogenic activity of multiple growth factors may contribute to mammary gland ductal morphogenesis as well as to breast cancer progression.
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PMID:Bone morphogenetic protein-4 strongly potentiates growth factor-induced proliferation of mammary epithelial cells. 1862 98

The stimulation of fibroblast growth factor receptors (FGFRs) with distinct FGF ligands generates specific cellular responses. However, the mechanisms underlying this paradigm have remained elusive. Here, we show that FGF-7 stimulation leads to FGFR2b degradation and, ultimately, cell proliferation, whereas FGF-10 promotes receptor recycling and cell migration. By combining mass-spectrometry-based quantitative proteomics with fluorescence microscopy and biochemical methods, we find that FGF-10 specifically induces the rapid phosphorylation of tyrosine (Y) 734 on FGFR2b, which leads to PI3K and SH3BP4 recruitment. This complex is crucial for FGFR2b recycling and responses, given that FGF-10 stimulation of either FGFR2b_Y734F mutant- or SH3BP4-depleted cells switches the receptor endocytic route to degradation, resulting in decreased breast cancer cell migration and the inhibition of epithelial branching in mouse lung explants. Altogether, these results identify an intriguing ligand-dependent mechanism for the control of receptor fate and cellular outputs that may explain the pathogenic role of deregulated FGFR2b, thus offering therapeutic opportunities.
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PMID:Functional proteomics defines the molecular switch underlying FGF receptor trafficking and cellular outputs. 2401 90

Purpose: Evidence indicates that long noncoding RNAs (lncRNA) possess important roles in various cellular processes and that dysregulation of lncRNAs promotes tumor progression. However, the expression patterns and biological functions of many specific lncRNAs in breast cancer remain to be determined. Methods: Quantitative real-time polymerase chain reaction was performed to detect Linc00460, miR-489-5p and FGF7 expression. Protein levels were determined using Western blot. MTT and colony formation assay were used to measure cell proliferation. Transwell assays were conducted to determine cell migration and invasion. Luciferase reporter assays were carried out to assess the interaction between miR-489-5p and Linc00460 or FGF7. Biotin pull-down assay was used to detect the direct interaction between miR-489-5p and Linc00460. In vivo experiments were performed to measure tumor formation and lung metastasis. Results: We demonstrated that lncRNA Linc00460 was upregulated in breast cancer, and its expression level was positively associated with lymphatic metastasis and poor overall survival. Forced expression of Linc00460 increased, whereas Linc00460 silencing decreased, breast cancer cell viability, migration and invasion both in vitro and in vivo. Linc00460 was identified as a direct target of miR-489-5p, which further targeted FGF7 and exerted oncogenic functions in breast cancer. Mechanistically, Linc00460 served as a competing endogenous RNA of FGF-7 mRNA by sponging miR-489-5p, resulting in upregulated FGF7 expression and AKT activity. Notably, forced expression of miR-489-5p abrogated Linc00460-mediated oncogenic behavior and activation of the FGF7-AKT pathway in breast cancer cells. Conclusion: We have demonstrated that Linc00460 promotes breast cancer progression partly through the miR-489-5p/FGF7/AKT axis.
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PMID:Long noncoding RNA Linc00460 promotes breast cancer progression by regulating the miR-489-5p/FGF7/AKT axis. 3130 41


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