Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells

Stavik, Benedicte; Skretting, Grethe; Sletten, Marit; Sandset, Per Morten; Iversen, Nina

doi:10.1002/mc.20679

Cited by 25 publications

(40 citation statements)

References 29 publications

(48 reference statements)

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“…The ability of breast cancer cells to express some of those genes was also described in previous reports [Pederson et al, 1999;Hunt et al, 2001;Lau et al, 2007]. Furthermore, SK-BR-3 and T47D were able to express TNF-a, which is in line with previous findings [Mrusek et al, 2005;Stavik et al, 2010].…”

supporting

confidence: 89%

Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines

Costa‐Rodrigues

Moniz

Teixeira

et al. 2012

J of Cellular Biochemistry

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Breast cancer frequently metastasizes to the bone, often leading to the formation of osteolytic lesions. This work compares the paracrine-induced osteoclastogenesis mediated by four human breast cancer cell lines, the estrogen-receptor positive T47D and MCF-7 and the estrogen-negative SK-BR-3 and Hs-578T cell lines. Human osteoclast precursor cells were cultured in the presence of conditioned media from the breast cancer cell lines (10% and 20%), collected at different culture periods (48 h, 7 days, and 14 days). Cultures performed in the absence or the presence of M-CSF and RANKL served as negative and positive control, respectively. Results showed that the cell lines differentially expressed several osteoclastogenic genes. All cell lines exhibited a significant osteoclastogenic potential, evidenced by a high TRAP activity and number of osteoclastic cells, expression of several osteoclast-related genes, and, particularly, a high calcium phosphate resorption activity. Differences among the osteoclastogenic potential of the cell lines were noted. T47D and MCF-7 cell lines displayed the highest and the lowest osteoclastogenic response, respectively. Despite the variability observed, MEK and NF-κB signaling pathways, and, at a lesser extent, PGE2 production, seemed to have a central role on the observed osteoclastogenic response. In conclusion, the tested breast cancer cell lines exhibited a high osteoclastogenic potential, although with some variability on the cell response profile, a factor to be considered in the development of new therapeutic approaches for breast cancer-induced bone metastasis.

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supporting

confidence: 89%

Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines

Costa‐Rodrigues

Moniz

Teixeira

et al. 2012

J of Cellular Biochemistry

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“…Stable cell lines with TFPI upregulated were established as previously described [18]. In short, cDNAs encoding TFPIα or TFPIβ were cloned into the pcDNA3.1/V5/His-pTOPO vector (Invitrogen Life Technology, Carlsbad, CA) and transfected into SK-BR-3 wild type cells using Lipofectamine 2000.…”

Section: Methodsmentioning

confidence: 99%

“…For validation of the mRNA data, samples were prepared as previously reported [18] using assays detecting ASCL1 (Hs00269932_m1), BCL2 (Hs00608023_m1), EGFR (Hs01076076_m1), ERBB2 (Hs01001580_m1), DOCK11 (Hs00376176_m1), GPNMB (Hs01095679_m1), IFI27 (Hs00271467_m1), IFIT2 (fwd primer: 5'- CCCAGCATCAGCCACACT-‘3, rev primer: 5’- AAAAACCATGAATTTGTATTGTTTTAATTGCACAA-‘3, reporter: 5’- CTGGGTTGGAAAATGT-‘3), IFITM1 (fwd primer: 5’- GGCTCTGTGACAGTCTACCATATT-‘3, rev primer: 5’- GCTATGGGCGGCTACTAGTAAC-‘3, reporter: 5’- CCCGTTTTTCCTGTATTATC-‘3), IGF1R (Hs00609566_m1), MX1 (fwd primer: 5’- TGCTGAACATCACAGCTTATTTCCT-‘3, rev primer: 5’- CGGCACTCATGCTCCTAAAACA-‘3, reporter: 5’- CTGGGTTTGTGAAGGGACAT-‘3), NFKBIA (Hs00153283_m1), PGR (Hs01556702_m1), RET (Hs01120030_m1), SERPINE1 (Hs00167155_m1), and STAT3 (Hs00234174_m1). For validation of the miRNA results, samples were prepared using the TaqMan MicroRNA RT kit (Applied Biosystems Life Technologies) as described by the manufacturer with assays detecting let-7d (#002283), miR-103 (#000439), miR-106b (#000442), miR-126 (#002228), miR-135a (#000460), miR-135b (#002261), miR-21 (#000397), miR-29c (#000587), miR-205 (#000509), miR-222 (#002276), miR-342-3p (#002260), miR-365 (#001020), and miR-652 (#002352).…”

Section: Methodsmentioning

confidence: 99%

“…Several cancer tissues and cell lines have been shown to express TFPI [14], [15], and TFPI treatment has been reported to reduce tumor growth and metastasis in vivo [16], [17]. We recently reported that overexpression of TFPIα or TFPIβ in SK-BR-3 breast cancer cells resulted in pro-apoptotic and anti-proliferative effects of either isoform in vitro [18], but the mechanism behind the effect of TFPI is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

et al. 2012

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Emerging evidence indicate a new role of TFPI in cancer biology. We recently reported that both isoforms of TFPI induced apoptosis and inhibited proliferation of cancer cells. The signaling pathway(s) mediating the effects of TFPI is, however, presently still unclear. Our goal was to further investigate the cellular processes affected by TFPI and to get insight into the molecular mechanisms involved in the effects of TFPI, using a global gene expression study approach. TFPIα or TFPIβ cDNA were transfected into SK-BR-3 breast cancer cells for stable overexpression. Global mRNA and microRNA (miRNA) expressions were measured and functional annotation of the differentially expressed genes and miRNAs according to gene ontology terms was conducted. Selected results were validated using qRT-PCR and Western blot. A total of 242 and 801 mRNA transcripts and 120 and 46 miRNAs were differentially expressed in cells overexpressing TFPIα or TFPIβ, respectively. Overexpression of either isoform significantly affected the expression of genes involved in cell development (apoptosis, cell movement, migration, invasion, colony formation, growth, and adhesion) and immune response. Network analyses revealed biological interactions between these genes and implied that several of the genes may be involved in both processes. The expression profiles also correlated significantly with clinical phenotype and outcome. Functional cluster analyses indicated altered activity of the epidermal growth factor receptor, small GTPases, and the NF-κB and JAK/STAT cascades when TFPI was overexpressed, and increased activity of the transcription factors NF-κB and Elk-1 and phospho-Akt levels was observed. Integrated mRNA-miRNA analyses showed that 19% and 32% of the differentially expressed genes in cells overexpressing TFPIα or TFPIβ, respectively, may have been regulated by miRNAs. Overexpression of TFPI in breast cancer cells affected the expression of mRNAs and miRNAs involved in processes facilitating cancer cell growth and immunologic response, possibly by signal transduction involving the EGFR pathway.

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“…In keeping with this observation, multiple breast cancer cell lines also express TFPIα and TFPIβ [68] . Overexpression of both TFPI-1 isoforms induces apoptosis of breast cancer cells [69] . Downregulation of TFPI-1 increases cell motility and breast cancer cell invasiveness [70] , suggesting that TFPI-1 acts as a suppressor of breast cancer phenotypes.…”

Section: Tissue Factor Pathway Inhibitors: Negative Regulators Of Tf-mentioning

confidence: 99%

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

Koizume

Miyagi

2014

WJCO

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Breast cancer is a leading cause of cancer death in women, worldwide. Fortunately, breast cancer is relatively chemosensitive, with recent advances leading to the development of effective therapeutic strategies, significantly increasing disease cure rate. However, disease recurrence and treatment of cases lacking therapeutic molecular targets, such as epidermal growth factor receptor 2 and hormone receptors, referred to as triple-negative breast cancers, still pose major hurdles in the treatment of breast cancer. Thus, novel therapeutic approaches to treat aggressive breast cancers are essential. Blood coagulation factor VII (fVII) is produced in the liver and secreted into the blood stream. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. TF is overexpressed in breast cancer tissues. The TF-fVII complex may be formed in the absence of injury, because fVII potentially exists in the tissue fluid within cancer tissues. The active form of this complex (TF-fVIIa) may stimulate the expression of numerous malignant phenotypes in breast cancer cells. Thus, the TF-fVII pathway is a potentially attractive target for breast cancer treatment. To date, a number of studies investigating the mechanisms by which TF-fVII signaling contributes to breast cancer progression, have been conducted. In this review, we summarize the mechanisms controlling TF and fVII synthesis and regulation in breast cancer cells. Our current understanding of the TF-fVII pathway as a mediator of breast cancer progression will be also described. Finally, we will discuss how this knowledge can be applied to the design of future therapeutic strategies. Key words: Breast cancer; Blood coagulation; Tissue factor; Coagulation factor VII; Gene regulation; Therapeutic strategy Core tip: Breast cancer is a worldwide problem. Difficulties with treating the disease and its recurrence persist due, in part, to a lack of therapeutic molecular targets. Blood coagulation factor VII (fVII) is generally produced in the liver. Tissue factor (TF), the cellular receptor for fVII, is an integral membrane protein that plays key roles in the extrinsic coagulation cascade. Formation of the TF-fVII complex causes contributes to the malignant phenotype of breast cancer cells. In this review, we summarize the breast cancer biology associated with the TF-fVII pathway. Further, we will discuss how these mechanisms can be targeted as therapeutics for this aggressive disease.Koizume S, Miyagi Y. Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets.

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Overexpression of both TFPIα and TFPIβ induces apoptosis and expression of genes involved in the death receptor pathway in breast cancer cells

Cited by 25 publications

References 29 publications

Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines

Variability of the paracrine‐induced osteoclastogenesis by human breast cancer cell lines

TFPI Alpha and Beta Regulate mRNAs and microRNAs Involved in Cancer Biology and in the Immune System in Breast Cancer Cells

Breast cancer phenotypes regulated by tissue factor-factor VII pathway: Possible therapeutic targets

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