scholarly journals Heregulin-Dependent Delay in Mitotic Progression Requires HER4 and BRCA1

2006 ◽  
Vol 26 (17) ◽  
pp. 6412-6424 ◽  
Author(s):  
Rebecca S. Muraoka-Cook ◽  
Laura S. Caskey ◽  
Melissa A. Sandahl ◽  
Debra M. Hunter ◽  
Carty Husted ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Breast Cancers ◽  
Human Breast ◽  
Independent Manner ◽  
Mitotic Delay

ABSTRACT HER4 expression in human breast cancers correlates with a positive prognosis. While heregulin inhibits the growth of HER4-positive breast cancer cells, it does so by undefined mechanisms. We demonstrate that heregulin-induced HER4 activity inhibits cell proliferation and delays G2/M progression of breast cancer cells. While investigating pathways of G2/M delay, we noted that heregulin increased the expression of BRCA1 in a HER4-dependent, HER2-independent manner. Induction of BRCA1 by HER4 occurred independently of the cell cycle. Moreover, BRCA1 expression was elevated in HER4-postive human breast cancer specimens. Heregulin stimulated c-Jun N-terminal kinase (JNK), and pharmacologic inhibition of JNK impaired heregulin-enhanced expression of BRCA1 and mitotic delay; inhibition of Erk1/2 did not. Knockdown of BRCA1 with small interfering RNA in a human breast cancer cell line interfered with HER4-mediated mitotic delay. Heregulin/HER4-dependent mitotic delay was examined further with an isogenic pair of mouse mammary epithelial cells (MECs) derived from mice harboring homozygous LoxP sites flanking exon 11 of BRCA1, such that one cell line expressed BRCA1 while the other cell line, after Cre-mediated excision, did not. BRCA1-positive MECs displayed heregulin-dependent mitotic delay; however, the isogenic BRCA1-negative MECs did not. These results suggest that heregulin-mediated growth inhibition in HER4-postive breast cancer cells requires BRCA1.

A Novel Naphthotriazolyl-4-oxoquinoline Derivative that Selectively Controls Breast Cancer Cells Survival Through the Induction of Apoptosis

2018 ◽  
Vol 18 (17) ◽  
pp. 1465-1474 ◽  
Author(s):  
Jessica R. Branco ◽  
Vanessa G. Oliveira ◽  
Amanda M. Esteves ◽  
Ingrid C. Chipoline ◽  
Miriam F.O. Lima ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast ◽  
Mcf 7

Background: Breast cancer is a major cause of death among women worldwide. Treatment for breast cancer involves the surgical removal of cancer tissue, followed by chemotherapy. Although the treatment is efficient, especially when the cancer is detected early, recurrence is common and is often resistant to the previous treatment. Therefore, a constant search for efficient and novel drugs for the treatment of breast cancer is mandatory. Recently, triazole derivatives have shown promising effects against different types of cancer, revealing these molecules as putative anticancer drugs. Experimental: We have synthesized a series of naphthotriazolyl-4-oxoquinoline derivatives and tested their activity against a human breast cancer cell line. Among the compounds tested, we identified a molecule that killed the human breast cancer cell line MCF-7 with minimal effects on its noncancer counterpart, MCF10A. This effect was seen after 24 hours of treatment and persisted for additional 24 hours after treatment withdrawal. After 1 hour of treatment, the compound, here named 12c, promoted a decrease in cell glucose consumption and lactate production. Moreover, the cells treated with 12c for 1 hour showed diminished intracellular ATP levels with unaltered mitochondrial potential and increased reactive oxygen species production. Additionally, apoptosis was triggered after treatment with the drug for 1 hour. All of these effects are only observed with MCF-7 cells, and not MCF10A. These data show that 12c has selective activity against breast cancer cells and is a potential candidate for a novel anticancer drug. Results and Conclusion: The naphthotriazolyl-4-oxoquinoline derivatives were obtained in good to moderate yields, and one of them, 12c, exhibited strong and selective antitumor properties. The antitumor mechanism involves inhibition of glycolysis, diminished intracellular ATP levels, induction of ROS production and triggering of apoptosis. These effects are all selective for cancer cells, since noncancer cells are unaffected, and these effects can only be attributed to the whole molecule, as different pharmacophoric groups did not reproduce these effects.

Pleiotrophin Secreted from Human Breast Cancer MCF-7-Ptn Cells Activates Stromal Fibroblasts, Induces Epithelial Island Formation, and Remodels the Microenvironment.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2568-2568 ◽  
Author(s):  
Masahiko Zuka ◽  
Yunchao Chang ◽  
Zhaoyi Wang ◽  
James R. Berenson ◽  
Thomas F. Deuel
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Breast Cancers ◽  
Human Breast ◽  
Nih3t3 Cells ◽  
Inappropriate Expression ◽  
Nih 3T3 ◽  
Mcf 7

Abstract Pleiotrophin (PTN, Ptn) is an 18 kD cytokine that is expressed in many human breast cancers and its gene is inappropriately expressed in cell lines derived from these breast cancers. To study the siginificance of inappropriate expression of Ptn in human breast cancer cells on surrounding stromal cells, we first compared nude mouse xenografts of MCF-7 and MCF-7-Ptn cells. MCF-7-Ptn cells lack the Receptor Protein Tyrosine Phosphatase (RPTP)b/z, the PTN receptor, and thus are not responsive to PTN through autocrine or paracrine stimulation. The MCF-7-Ptn cell xenografts grew rapidly whereas MCF-7 cells xenografts were barely detectable 6 weeks after injection. MCF-7-Ptn cells that were co-injected with equal numbers of NIH3T3 cells grew even more rapidly in the flanks of the nude mice. Surprisingly, the MCF-7-Ptn cell explants developed a morphological phenotype remarkably similar to that of the human invasive ductal carcinoma. We then co-cultured MCF-7 cells that express Ptn (MCF-7-Ptn cells) with NIH 3T3 cells. Secretion of PTN from MCF-7-Ptn cells induced formation of sharply defined clusters of MCF-7-Ptn cells, termed “epithelial islands”, that were surrounded by dense fibrous bands interspersed with NIH 3T3 cells that morphologically closely resemble carcinoma associated fibroblasts (CAFs). A striking increase in tropoelastin and expression of type IV procollagen mRNA was identified in NIH3T3 cells co-cultured with MCF-7-Ptn cells. Furthermore, different markers often resulting from stromal cell-carcinoma cell interactions in breast cancer, including protein kinase C (PKC)-d, and both human and murine matrix metalloproteinase (MMP) 9 were identified either in cells or in the culture media taken from MCF-7-Ptn/NIH3T3 cell co-cultures. The induction of these biochemical and morphological features in the co-cultures of MCF-7-Ptn and NIH3T3 cells was demonstrated to be Ptn expression dependent, PTN-secretion dependent, and NIH3T3 cell dependent. The data suggest that PTN secretion alone from human breast cancer cells with inappropriate expression of Ptn is sufficient to markedly remodel the microenvironment of the breast cancer cell and induce a morphological transition of the MCF-7-Ptn cells and NIH3T3 cells to patterns resembling breast carcinomas through activation of the PTN/RPTPb/z signaling pathway in NIH3T3 cells and reciprocal signaling between the carcinoma stromal cells and the PTN secreting breast cancer cells.

scholarly journals Long Noncoding RNA CAMTA1 Promotes Proliferation and Mobility of the Human Breast Cancer Cell Line MDA-MB-231 via Targeting miR-20b

2018 ◽  
Vol 26 (4) ◽  
pp. 625-635 ◽  
Author(s):  
Pengwei Lu ◽  
Yuanting Gu ◽  
Lin Li ◽  
Fang Wang ◽  
Xue Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cell Line ◽  
Long Noncoding Rna ◽  
Human Breast Cancer ◽  
Noncoding Rna ◽  
Breast Cancer Cells ◽  
Cancer Cell Line ◽  
Human Breast Cancer Cell ◽  
Human Breast

Breast cancer is a serious threat to women’s physical and psychological health. Long noncoding RNA CAMTA1 (lncCAMTA1) was believed to be related with tumor progression, but its role in breast cancer is not clear. The human breast cancer cell line MDA-MB-231 was used to investigate the effect of lncCAMTA1 on cell viability, migration/invasion, and apoptosis. The expression of lncCAMTA1, miR-20b, and VEGF in MDA-MB-231 were measured after corresponding transfections. Binding effects between lncCAMTA1 and miR-20b, miR-20b, and VEGF 3′-UTR were measured. The effects of miR-20b and VEGF on breast cancer cells were also assessed after transfections. The phosphorylation levels of the MAPK/ERK and JAK/STAT3 pathways were determined to assess the effect of VEGF. The results showed that lncCAMTA1 expression promoted cell viability and migration/invasion, while knockdown of lncCAMTA1 promoted cell apoptosis via binding with miR-20b. lncCAMTA1 negatively regulated miR-20b expression. VEGF was a target of miR-20b, leading to the modification of the phosphorylation levels of MAPK, ERK, JAK, STAT1, and STAT3. Our findings suggested that lncCAMTA1 might promote proliferation and mobility of human breast cancer cells via binding with miR-20b. VEGF was a direct target of miR-20b and regulated activation of the MAPK/ERK and JAK/STAT3 signaling pathways. Therefore lncCAMTA1 has potential as a novel cancer diagnostic marker and as a putative novel therapeutic target for breast cancer treatment.

scholarly journals The Extracts of Epilobium Parviflorum Inhibit MCF-7 Breast Cancer Cells

2021 ◽  
Vol 15 (1) ◽  
pp. 65-72
Author(s):  
Bhenaz Hatefi Kia ◽  
◽  
Sakineh Kazemi Noureini ◽  
Mohammad Reza Vaezi Kakhki ◽  
◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Hek293 Cells ◽  
Human Breast ◽  
Methanolic Extracts ◽  
Drug Development Research ◽  
Mcf 7

Background: Traditional medicine is inspiring in drug development research. Epilobium parviflorum extracts have shown promising therapeutic effects on prostate cancer cells. The similarities between breast and prostate cancers at molecular and metabolic levels prompted us to explore its effects on human breast cancer. Methods: The root, aerial parts and flowers of the plant were, collected and dried separately at ambient temperature and away from direct sunlight. The aquatic and methanolic extracts of each part was prepared. The effect of each extract on the growth of MCF-7 breast carcinoma cells and HEK293 normal cell line was evaluated, using MTT assay. Each experiment was repeated at least three times independently. The IC50 values for each treatment time point were analyzed, using ANOVA at P<0.05. Results: While none of the extracts had considerable toxicity on normal HEK293 cells, some of them showed varying levels of toxicity on the MCF-7 cells. The methanolic extracts were more cytotoxic than the aqueous counterpart. The roots’ methanolic extract showed the strongest cytotoxicity on the MCF-7 cells in a dose and exposure time dependent manner. The IC50 after 48 hours of treatment was determined at 73µg/ml. Conclusion: This study is the first to demonstrate that Epilobium parviflorum had a strong growth inhibiting property on MCF-7 cell line, as a potential model to treat human breast cancer cells. The most cytotoxic effect was noted for the methanolic root extract. Determination of the effective biochemical constituents of the extract against cancer cells is the focus of our future research.

scholarly journals Rhein Induces Apoptosis in Human Breast Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Ching-Yao Chang ◽  
Hong-Lin Chan ◽  
Hui-Yi Lin ◽  
Tzong-Der Way ◽  
Ming-Ching Kao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Her2 Overexpression ◽  
Breast Cancers ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Anthraquinone Derivatives ◽  
Mcf 7

Human breast cancers cells overexpressing HER2/neuare more aggressive tumors with poor prognosis, and resistance to chemotherapy. This study investigates antiproliferation effects of anthraquinone derivatives of rhubarb root on human breast cancer cells. Of 7 anthraquinone derivatives, only rhein showed antiproliferative and apoptotic effects on both HER2-overexpressing MCF-7 (MCF-7/HER2) and control vector MCF-7 (MCF-7/VEC) cells. Rhein induced dose- and time-dependent manners increase in caspase-9-mediated apoptosis correlating with activation of ROS-mediated activation of NF-κB- and p53-signaling pathways in both cell types. Therefore, this study highlighted rhein as processing anti-proliferative activity against HER2 overexpression or HER2-basal expression in breast cancer cells and playing important roles in apoptotic induction of human breast cancer cells.

Formation of Tissue Factor-Factor VIIa-Factor Xa Complex Promotes Survival of Human Breast Cancer Cells by Inhibition of Apoptosis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1942-1942
Author(s):  
Xiaofeng Jiang ◽  
Yan-Lin Guo ◽  
Michael E. Bromberg
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Factor Viia ◽  
Factor Xa ◽  
Human Breast ◽  
Apoptotic Effect ◽  
Mcf 7

Abstract Tissue factor (TF) is a transmembrane glycoprotein that initiates blood coagulation when complexed with factor VIIa (FVIIa). TF is constitutively expressed by a variety of tumor cells. Recently, TF has been shown to induce cellular signaling and promote tumor growth, angiogenesis, and metastasis. We showed previously that formation of TF-FVIIa-Factor Xa (FXa) complex induces cellular signaling in the Adr-MCF-7 cell line, a multidrug-resistant subline of the human breast cancer cell line, MCF-7 (Jiang et al. J. Thromb Haemost2: 2004; 93–101). This cell line has high endogenous expression of TF. Treatment of the Adr-MCF-7 cells with the combination of FVIIa (10 nM) and FX (150 nM) induces phosphorylation of p44/42 mitogen-activated protein kinase (MAPK) and protein kinase B (PKB), whereas no increase in the basal level of phosphorylation of these proteins occurs with treatment of the cells with FVIIa (10 nM) alone. In the present study, we investigated whether TF-FVIIa-induced signaling might alter apoptosis in human breast cancer cells. Apoptosis of the Adr-MCF-7 cells was induced by serum starvation for 5–7 days. Treatment of the cells with the combination of FVIIa (10 nM) and FX (150 nM), reduced apoptosis of the cells by nearly 50% compared with untreated, control cells using an ELISA that detects histone-DNA fragments. In contrast, FVIIa (10 nM) alone did not significantly prevent apoptosis. Pre-treatment of the Adr-MCF-7 cells with hirudin did not inhibit the anti-apoptotic effect of the combination of FVIIa and FX, whereas this effect could be completely blocked by either U0126 (10 μM), which inhibits p44/42 MAPK phosphorylation, or LY294002 (50 μM), which inhibits PKB phosphorylation. In addition, treatment of the Adr-MCF cells with the combination of FVIIa and FX led to a 50% increase in the level of the anti-apoptotic protein, survivin, compared with untreated cells by Western blot analysis. Results from this study indicate that formation of TF-FVIIa-FXa complex prevents apoptosis of breast cancer cells by a thrombin-independent pathway. Moreover, the anti-apoptotic effect of this signaling pathway involves both phosphorylation of p44/42 MAPK and PKB and might be mediated in part by an increase in cell survivin levels.

Expression of the WAVE (WASP Verprolin-homologous) molecules in human breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21061-21061
Author(s):  
H. Fernando ◽  
A. Chhabra ◽  
S. Davies ◽  
G. Watkins ◽  
H. Kynaston ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epithelial Cells ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Tissue Growth ◽  
Positive Staining ◽  
Breast Cancers ◽  
Human Breast ◽  
Ccn Family

21061 Background: WAVEs (WASP Verprolin-homologous) belongs to the CCN family which comprises of nine members, the cysteine-rich 61 (Cyr61/CCN1), connective tissue growth factor (CTGF/CCN2) and nephroblastoma over-expressed (Nov/CCN3), Wnt-induced secreted proteins(WISPs)1, 2 and 3 (CCN4–6) as well as the WAVE-1,2 and 3 (also known as CCN7–9 respectively). Some members of the CCN family, such as Cyr61 and CTGF are known to stimulate mitosis, adhesion, apoptosis, extracellular matrix production, cell migration and growth arrest in cancer cells including breast cancer cells. However, there is no knowledge of the expression pattern and the function of WAVEs in human breast cancer. Here, we report the expression of WAVE-1,-2 and -3 transcripts and proteins in relation to clinical and pathological characteristics in human breast cancer. Methods: The expression of the three WAVE molecules at the mRNA and protein levels in a cohort of 122 human breast cancers and 32 normal breast tissues were analysed and correlated with the patients’ clinical outcome. The respective transcripts were quantitative determined using real time RT-PCR and distribution of the proteins were investigated by immunohistochemical methods. Results: All three WAVE proteins were detected in mammary epithelial cells and are of cytoplasmic nature. Breast cancer cells from the tissues also displayed positive staining of the WAVE proteins, with WAVE-2 staining appears weaker compared with normal epithelial cells. WAVE-1 transcripts were expressed in significantly high levels (p=0.03) in high grade breast cancers. Low levels of WAVE-2 were associated with higher TNM staging (p=0.038 in TNM3 and p=0.017 in TNM4) and were also found in patients with poor prognosis. Interesting, a marginal reduction of WAVE-3 transcripts was seen in patients who developed systemic metastasis. No other significant associations were found between the WAVE1 and WAVE3 transcripts and the breast cancer cells. Conclusions: WAVEs are widely expressed in human mammary tissues and have a differential expression in human breast cancer with WAVE2 appearing to be associated with the aggressiveness of breast tumors. No significant financial relationships to disclose.

scholarly journals DCLK1 Plays a Metastatic-Promoting Role in Human Breast Cancer Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Heshu Liu ◽  
Tao Wen ◽  
Ying Zhou ◽  
Xiaona Fan ◽  
Tan Du ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cell Line ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Cancer Metastasis ◽  
Cancer Cell Line ◽  
Breast Cancer Metastasis ◽  
Human Breast Cancer Cells ◽  
Human Breast

Background. Doublecortin-like kinase 1 (DCLK1) has been universally identified as a cancer stem cell (CSC) marker and is found to be overexpressed in many types of cancers including breast cancer. However, there is little data regarding the functional role of DCLK1 in breast cancer metastasis. In the present study, we sought to investigate whether and how DCLK1 plays a metastatic-promoting role in human breast cancer cells.Methods. We used Crispr/Cas9 technology to knock out DCLK1 in breast cancer cell line BT474, which basically possesses DCLK1 at a higher level, and stably overexpressed DCLK1 in another breast cancer cell line, T47D, that basically expresses DCLK1 at a lower level. We further analyzed the alterations of metastatic characteristics and the underlying mechanisms in these cells.Results. It was shown that, compared with the corresponding control cells, DCLK1 overexpression led to an increase in metastatic behaviors including enhanced migration and invasion of T47D cells. By contrast, forced depletion of DCLK1 drastically inhibited these metastatic characteristics in BT474 cells. Mechanistically, the epithelial-mesenchymal transition (EMT) program, which is critical for cancer metastasis, was prominently activated in DCLK1-overexpressing cancer cells, evidenced by a decrease in an epithelial marker ZO-1 and an enhancement in several mesenchymal markers including ZEB1 and Vimentin. In addition, DCLK1 overexpression induced the ERK MAPK pathway, which resultantly enhanced the expression of MT1-MMP that is also involved in cancer metastasis. Knockout of DCLK1 could reverse these events, further supporting a metastatic-promoting role for DCLK1.Conclusions. Collectively, our data suggested that DCLK1 overexpression may be responsible for the increased metastatic features in breast cancer cells. Targeting DCLK1 may become a therapeutic option for breast cancer metastasis.

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