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1.
Overexpression of platelet-derived growth factor receptor α in breast cancer is associated with tumour progression
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Introduction
Receptor tyrosine kinases have been extensively studied owing to their frequently abnormal activation in the development and progression of human cancers. Platelet-derived growth factor receptors (PDGFRs) are receptors with intrinsic tyrosine kinase activity that regulate several functions in normal cells and are widely expressed in a variety of malignancies. After the demonstration that gastrointestinal stromal tumours without c-Kit mutations harbour PDGFR-α-activating mutations and that PDGFR-α is also a therapeutic target for imatinib mesylate, the interest for this receptor has increased considerably. Because breast cancer is one of the most frequent neoplasias in women worldwide, and only one study has reported PDGFR-α expression in breast carcinomas, the aim of this work was to investigate the potential significance of PDGFR-α expression in invasive mammary carcinomas. 相似文献2.
To estimate the clinical significance of estrogen receptor (ER) β in breast cancer we reviewed some reports and compared them
with our preliminary results. The structure of ER β is similar to that of ER α. The DNA binding domain of ER β is 96% conserved
compared with ER α, and the ligand binding domain shows 58% conserved residues, suggesting that both receptors can bind estrogen
responsive elements on target genes and that they may also bind similar ligand. The target tissues of ER β such as testis,
prostate, lung, brain, thymus, and ovary, are different from those of ER α, ovary, uterus, endometrium, and breast. Although
the function of ER β in breast cancer progression is not well understood, 30-50% of breast cancers may express ER β mRNA signals.
Additionally, ER β may be a useful prognostic factor in patients with breast cancer, because tumors that co-expressed ER α
and ER β might be node positive and tend to be of higher grade. Further characterization of the function of ER β and its isoforms
in breast cancer is warranted. 相似文献
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Speirs V 《Breast cancer research : BCR》2008,10(5):111
Controversy surrounds the potential clinical importance of oestrogen receptor (ER)β in breast cancer, and three recent papers have sought to resolve this. In the present issue of Breast Cancer Research Novelli and colleagues explored the significance of ERβ1 expression in 936 breast cancer patients, and they showed diverse relationships according to lymph node status. A second paper examined 442 breast cancers in which ERβ1 was an independent predictor of recurrence, disease-free survival and overall survival. Finally a third paper showed that ERβ2 was a powerful prognostic indicator in 757 breast cancers but this was dependent on cellular location, with nuclear ERβ2 expression predicting good survival whilst cytoplasmic expression predicted worse outcome. These papers point to a clinical role for ERβ in breast cancer and shall be discussed. 相似文献
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Interleukin 1 (IL-1) is a pluripotent cytokine that promotes inflammation, angiogenesis, tumor growth andmetastasis in experimental models; its presence in some human cancers is associated with tumor progression. Alex-ander et al. recently reported that inhibition of IL-1 by its receptor antagonist (IL-1Ra) retarded growth of IL-1-ex-pressing human cancer xenografts in nude mice (Clin Cancer Res 2006, 12:1088 ~1096). IL-1 mRNA and pro-tein levels were determined in clinical tumor samples… 相似文献
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Andrea Manni Daniel Trout Michael F. Verderame Sharlene Washington David Mauger Laurence Demers 《Breast cancer research and treatment》2001,68(2):139-146
We have previously shown that ornithine decarboxylase (ODC) overexpression enhances the transforming effects of HER-2neu and epidermal growth factor (EGF) in normal MCF-10A human breast epithelial cells. Our data suggest that such potentiation may be mediated by activation of the mitogen-activated protein kinase (MAPK) pathway and, possibly, STAT signalling. To further explore the interaction between the polyamine pathway and EGF/HER-2neu signalling in this system, we inhibited endogenous ODC activity with -difluoromethylornithine (DFMO) and assessed the effects of this blockade on the expression of EGF receptors (EGFR) and HER-2neu as well as activation of downstream EGF target genes. We found that DFMO administration to MCF-10A cells increased EGF-R mRNA and protein levels in a dose-response fashion, while HER-2neu expression was not affected. The effect of DFMO was mediated through polyamine depletion since it could be reversed by exogenous putrescine administration. Our results also indicated that the increase in EGFR induced by DFMO was not a non-specific consequence of inhibition of cell proliferation. The upregulated EGFRs were functional since they could be phosphorylated by EGF and they were able to promote phosphorylation of downstream signalling molecules including ERK, STAT-3, and STAT-5. We propose that physiologic levels of ODC activity may be critical for regulation of a yet undefined signalling pathway, whose blockade by DFMO leads to a compensatory increase in functional EGFR. 相似文献
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Mauro LV Dalurzo M Carlini MJ Smith D Nuñez M Simian M Lastiri J Vasallo B Bal de Kier Joffé E Pallotta MG Puricelli L 《Oncology reports》2010,24(5):1331-1338
As 20% of stage I NSCLC patients develop recurrent and often incurable cancer, the identification of prognostic markers has a meaningful clinical application. The biological significance of steroid hormone and EGF receptors, able to regulate key physiological functions, remains elusive in NSCLC. Our aim was to investigate the prognostic input of estrogen receptors (ERα, ERβ), progesterone receptors (PR) and EGFR in tumors from 58 stage I NSCLC patients. Antigen expression was analyzed by immunohistochemistry. Prognostic evaluation was performed with the multivariate Cox model. We found that about 70 and 40% of samples expressed ERα or ERβ at cytoplasmic or nuclear level, respectively. Besides, only 12.1% of samples weakly expressed nuclear PR and 62.7% showed membrane EGFR staining. Correlation studies indicated an inverse association between EGFR expression and smoking status (p<0.01). Multivariate studies showed that the lack of nuclear ERβ or the loss of EGFR expression were independent prognosis markers associated with shorter overall survival. We also found that patients whose tumors were negative for these two biomarkers presented the worst outcome. In conclusion, our findings could be useful for selecting stage I NSCLC patients with poor prognosis to apply an earlier treatment that impacts on survival. 相似文献
8.
O Shinto M Yashiro H Kawajiri K Shimizu T Shimizu A Miwa K Hirakawa 《British journal of cancer》2010,102(5):844-851
Background:
Gastric cancer cells frequently metastasise, partly because of their highly invasive nature. Transforming growth factor-β (TGF-β) receptor signalling is closely associated with the invasion of cancer cells. The aim of this study was to clarify the effect of a TGF-β receptor (TβR) phosphorylation inhibitor on the invasiveness of gastric cancer cells.Methods:
Four gastric cancer cell lines, including two scirrhous-type cell lines and two non-scirrhous-type cell lines, were used. A TβR type I (TβR-I) kinase inhibitor, Ki26894, inhibits the phosphorylation of Smad2 at an ATP-binding site of TβR-I. We investigated the expression levels of TβR and phospho-Smad2, and the effects of TGF-β in the presence or absence of Ki26894 on Smad2 phosphorylation, invasion, migration, epithelial-to-mesenchymal transition (EMT), Ras homologue gene family member A (RhoA), ZO-2, myosin, and E-cadherin expression of gastric cancer cells.Results:
TβR-I, TβR-II, and phospho-Smad2 expressions were found in scirrhous gastric cancer cells, but not in non-scirrhous gastric cancer cells. Ki26894 decreased Smad2 phosphorylation induced by TGF-β1 in scirrhous gastric cancer cells. Transforming growth factor-β1 upregulated the invasion, migration, and EMT ability of scirrhous gastric cancer cells. Transforming growth factor-β1 significantly upregulated the activity of RhoA and myosin phosphorylation, whereas TGF-β1 decreased ZO-2 and E-cadherin expression in scirrhous gastric cancer cells. Interestingly, Ki26894 inhibited these characteristics in scirrhous gastric cancer cells. In contrast, non-scirrhous gastric cancer cells were not affected by TGF-β1 or Ki26894 treatment.Conclusion:
A TβR-I kinase inhibitor decreases the invasiveness and EMT of scirrhous gastric cancer cells. Ki26894 is therefore considered to be a promising therapeutic compound for the metastasis of scirrhous gastric carcinoma. 相似文献9.
Musgrove EA 《Breast cancer research : BCR》2004,6(2):65-68
Recent data have suggested the epidermal-growth-factor receptor (EGFR) as a point of convergence for several different classes of receptor. Civenni and colleagues have now demonstrated crosstalk between Wnt signalling and the EGFR, showing that in breast epithelial cells Wnts activate downstream targets of the EGFR, including cyclin D1. Given the role of members of these pathways in the aetiology of breast cancer and as markers of outcome and potential therapeutic targets in breast cancer, this observation has a number of potential implications important for both the basic biology of breast cancer and the clinical management of the disease. 相似文献
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Recent data have suggested the epidermal-growth-factor receptor (EGFR) as a point of convergence for several different classes
of receptor. Civenni and colleagues have now demonstrated crosstalk between Wnt signalling and the EGFR, showing that in breast
epithelial cells Wnts activate downstream targets of the EGFR, including cyclin D1. Given the role of members of these pathways
in the aetiology of breast cancer and as markers of outcome and potential therapeutic targets in breast cancer, this observation
has a number of potential implications important for both the basic biology of breast cancer and the clinical management of
the disease. 相似文献
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Hypoxia-inducible factor-1α and vascular endothelial growth factor expression in circulating tumor cells of breast cancer patients
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Galatea Kallergi Harris Markomanolaki Vicky Giannoukaraki Maria A Papadaki Areti Strati Evi S Lianidou Vassilis Georgoulias Dimitris Mavroudis Sofia Agelaki 《Breast cancer research : BCR》2009,11(6):R84-12
Introduction
The detection of peripheral blood circulating tumor cells (CTCs) and bone marrow disseminated tumor cells (DTCs) in breast cancer patients is associated with a high incidence of disease relapse and disease-related death. Since hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) play an important role in angiogenesis and tumor progression, the purpose of the current study was to investigate their expression in CTCs. 相似文献16.
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We studied the chemopreventive efficacy of indole-3-carbinol (I3C), a phytochemical found in cruciferous vegetables, to inhibit tobacco carcinogen-induced lung adenocarcinoma in A/J mice when given following post-initiation or progression protocol. Moreover, we assessed the potential mechanisms responsible for the anticancer effects of I3C. Post-initiation administration of I3C decreased the multiplicity of surface tumors as well as all forms of histopathological lesions, including adenocarcinoma, whereas administration of the compound during tumor progression failed to decrease the multiplicity of surface tumors and early forms of microscopic lesions but reduced the frequency of adenocarcinoma. Mechanistic studies in A549 lung adenocarcinoma cells indicated that the lung cancer preventive effects of I3C are mediated, at least in part, via modulation of the receptor tyrosine kinase/PI3K/Akt signaling pathway. 相似文献
18.
In-utero exposures and breast cancer risk: joint effect of estrogens and insulin-like growth factor?
Schernhammer ES 《Cancer causes & control : CCC》2002,13(6):505-508
Initial evidence from observational studies led to the suggestion that high maternal estrogens in-utero are central factors in the development of adult breast cancer. Subsequently, several studies attempted to illuminate this hypothesis, but few of the more detailed observational studies show a clear and strong association between prenatal estrogen exposure and breast cancer risk in adulthood. To date, the potential underlying biological mechanisms remain unclear and controversial. However, recent observations of a relation between insulin-like growth factor-1 (IGF-1) and breast cancer risk may shed new light on the role of in-utero exposure, early growth, and risk of breast cancer. More research is needed to elucidate this potential mechanism. 相似文献
19.
Massabeau C Sigal-Zafrani B Belin L Savignoni A Richardson M Kirova YM Cohen-Jonathan-Moyal E Mégnin-Chanet F Hall J Fourquet A 《Breast cancer research and treatment》2012,132(1):259-266
There is evidence that aspirin use reduces the risk of breast cancer. Increased mammographic density is known to be associated
with increased breast cancer risk. Little is known about the association between mammographic density and aspirin or other
non-steroidal anti-inflammatory drug (NSAID) use, but it is possible that the association between aspirin use and breast cancer
risk might be due to the effect of aspirin on mammographic density. Multiple linear regression was used to investigate the
association between measures of mammographic density and the use, frequency, and duration of aspirin and other NSAIDs such
as paracetamol (acetaminophen), arthritis medication, and other over-the-counter or doctor-prescribed pain medications in
3286 women from the Australian Mammographic Density Twins and Sisters Study and the Genes Behind Endometriosis Study. We found
no association between either dense area or percent dense area with any of the NSAIDs examined (all P > 0.06). If aspirin is reducing the breast cancer risk in women, it is likely doing so via a different pathway other than
mammographic density measures that predict breast cancer risk. 相似文献
20.
Michael K Wendt Molly A Taylor Barbara J Schiemann Khalid Sossey-Alaoui William P Schiemann 《Breast cancer research : BCR》2014,16(2):R24