scholarly journals Regulation of thrombospondin-1 by natural and synthetic progestins in human breast cancer cells

2009 ◽  
Vol 16 (3) ◽  
pp. 809-817 ◽  
Author(s):  
Salman M Hyder ◽  
Yayun Liang ◽  
Jianbo Wu ◽  
Vanessa Welbern
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
P53 Protein ◽  
Endothelial Cell Proliferation ◽  
Ru 486 ◽  
Thrombospondin 1 ◽  
Treated Breast ◽  
Endothelial Growth Factor ◽  
Natural And Synthetic

Our recent studies show that progestins induce vascular endothelial growth factor (VEGF) in breast cancer cells that express mutant p53 protein. Here, we show that natural and synthetic progestins also induce thrombospondin-1 (TSP-1) mRNA and protein in T47-D and BT-474 breast cancer cells. Antiprogestin RU-486 inhibits the induction of VEGF and TSP-1 by progestins, suggesting that this effect of progestin is mediated by the progesterone receptor (PR). Actinomycin-D, but not puromycin, also blocks progestin-dependent induction of TSP-1. A putative progestin-response element was identified in the human TSP-1 promoter, which is consistent with the hypothesis that a progestin–PR complex might directly regulate transcription of the TSP-1 gene in human cells. Conditioned medium from progestin-treated breast cancer cells stimulates endothelial cell proliferation in the absence though not in the presence of antibody to TSP-1, indicating that TSP-1 secreted by breast cancer cells could be pro-angiogenic. Since tumor cell-derived TSP-1 has the potential to promote angiogenesis in the tumor microenvironment, it could be a potential target for breast cancer therapy.

scholarly journals Vascular endothelial growth factor induces proliferation of breast cancer cells and inhibits the anti-proliferative activity of anti-hormones

2006 ◽  
Vol 13 (3) ◽  
pp. 905-919 ◽  
Author(s):  
Yayun Liang ◽  
Rolf A Brekken ◽  
Salman M Hyder
Keyword(s):  
Breast Cancer ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cell Lines ◽  
Breast Cancer Cells ◽  
Vascular Endothelial ◽  
Ru 486 ◽  
Endothelial Growth Factor

Increased levels of vascular endothelial growth factor (VEGF) are associated with a poor response of breast cancer to anti-hormone treatment. Although VEGF is regarded as an endothelial-specific growth factor, recent reports have shown that VEGF can promote proliferation of other cell types, including breast tumor cells. We have characterized the proliferative effects of VEGF in breast cancer cell lines that are commonly used for understanding the role of estrogens, progestins, and anti-hormones on tumor growth. Since steroid hormones can increase the level of VEGF in certain breast cancer cells, we evaluated the effects of exogenous VEGF on the growth-suppressive effects of anti-estrogen (ICI 182,780) and RU-486 (anti-progestin mifepristone) in human breast cancer cells. VEGF165 and VEGF121 increased the proliferation of tumor cell lines that expressed VEGFR-2 (VEGF receptor 2) (flk/kdr) via the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway. Furthermore, VEGF induced the expression of the anti-apoptotic protein Bcl-2 and blocked down-regulation of Bcl-2 by ICI 182,780 and induced Bcl-2 in BT-474 and T47-D cells even in the presence of RU-486. Increased Bcl-2 levels in response to VEGF were associated with increased proliferation and survival of tumor cells even in the presence of anti-hormones. These results suggest that VEGF stimulates proliferation of VEGFR2-positive tumor cells, promotes survival via the expression and activity of Bcl-2 and overrides the growth-suppressive effects of anti-hormones. This represents a potential explanation for anti-hormone resistance and tumor progression in clinical samples. Thus, it may be useful to use combined modality treatment involving anti-hormones and anti-angiogenic agents to treat breast cancers that express elevated levels of VEGF.

Beneficial effects of the redox-active complex Cu[15]pyN5 in doxorubicin-treated breast cancer cells

2012 ◽  
Vol 53 ◽  
pp. S119-S120
Author(s):  
A.S. Fernandes⁎ ◽  
M. Cipriano ◽  
J. Costa ◽  
M.F. Cabral ◽  
J. Miranda ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Active Complex ◽  
Beneficial Effects ◽  
Redox Active ◽  
Treated Breast ◽  
Treated Breast Cancer

VITAMIN D DERIVATIVES IN COMBINATION WITH 9-cis RETINOIC ACID PROMOTE ACTIVE CELL DEATH IN BREAST CANCER CELLS

1995 ◽  
Vol 14 (3) ◽  
pp. 391-394 ◽  
Author(s):  
S Y James ◽  
A G Mackay ◽  
K W Colston
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
P53 Protein ◽  
Protein A ◽  
Therapeutic Implications ◽  
Protein Levels ◽  
Mcf 7

ABSTRACT The effects of the novel vitamin D analogue, EB1089 alone, or in combination with the retinoid, 9-cis retinoic acid (9-cis RA) on indices of apoptosis in MCF-7 breast cancer cells have been examined. EB1089 was capable of reducing bcl-2 protein, a suppressor of apoptosis, and increasing p53 protein levels in MCF-7 cell cultures following 96h treatment. In the presence of 9-cis RA, EB1089 acted to further enhance the down-regulation and up-regulation of bcl-2 and p53 respectively. Furthermore, EB1089 induces DNA fragmentation in MCF-7 cells, a key feature of apoptosis, alone and in combination with 9-cis RA in situ. The observation that EB1089 and 9-cis RA act in a cooperative manner to enhance induction of apoptosis in these cells may have therapeutic implications.

scholarly journals MiR-9-3p regulates the biological functions and drug resistance of gemcitabine-treated breast cancer cells and affects tumor growth through targeting MTDH

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yike Wang ◽  
Lifeng Dong ◽  
Fang Wan ◽  
Fangfang Chen ◽  
Dianlei Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Resistance ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Biological Functions ◽  
Qrt Pcr ◽  
Treated Breast ◽  
Cancer Tissues ◽  
Treated Breast Cancer

AbstractThis study explored the role of MTDH in regulating the sensitivity of breast cancer cell lines to gemcitabine (Gem) and the potential miRNAs targeting MTDH. The expression of MTDH in cancer tissues and cells was detected by immunohistochemical staining or qRT-PCR. The target genes for MTDH were predicted by bioinformatics and further confirmed by dual-luciferase reporter assay and qRT-PCR. Cancer cells were transfected with siMTDH, MTDH, miR-9-3p inhibitor, or mimics and treated by Gem, then CCK-8, colony formation assay, tube formation assay, flow cytometry, wound healing assay, and Transwell were performed to explore the effects of MTDH, miR-9-3p, and Gem on cancer cell growth, apoptosis, migration, and invasion. Expressions of VEGF, p53, cleaved caspase-3, MMP-2, MMP-9, E-Cadherin, N-Cadherin, and Vimentin were determined by Western blot. MTDH was high-expressed in cancer tissues and cells, and the cells with high-expressed MTDH were less sensitive to Gem, while silencing MTDH expression significantly promoted the effect of Gem on inducing apoptosis, inhibiting cell migration, invasion, and growth, and on regulating protein expressions of cancer cells. Moreover, miR-9-3p had a targeted binding relationship with MTDH, and overexpressed miR-9-3p greatly promoted the toxic effects of Gem on cancer cells and expressions of apoptosis-related proteins, whereas overexpressed MTDH partially reversed such effects of overexpressed miR-9-3p. The study proved that miR-9-3p regulates biological functions, drug resistance, and the growth of Gem-treated breast cancer cells through targeting MTDH.

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