Browsing by Subject "breast cancer cells"

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    CD44+/CD24- breast cancer cells exhibit enhanced invasive properties: an early step necessary for metastasis
    (BMC, 2006) Sheridan, Carol; Kishimoto, Hiromitsu; Fuchs, Robyn K; Mehrotra, Sanjana; Bhat-Nakshatri, Poornima; Turner, Charles H; Goulet, Robert; Badve, Sunil; Nakshatri, Harikrishna
    Introduction A subpopulation (CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. The aim of this study was to investigate whether this subpopulation of cancer cells has the unique ability to invade, home, and proliferate at sites of metastasis. Methods CD44 and CD24 expression was determined by flow cytometry. Northern blotting was used to determine the expression of proinvasive and 'bone and lung metastasis signature' genes. A matrigel invasion assay and intracardiac inoculation into nude mice were used to evaluate invasion, and homing and proliferation at sites of metastasis, respectively. Results Five among 13 breast cancer cell lines examined (MDA-MB-231, MDA-MB-436, Hs578T, SUM1315, and HBL-100) contained a higher percentage (>30%) of CD44+/CD24- cells. Cell lines with high CD44+/CD24- cell numbers express basal/mesenchymal or myoepithelial but not luminal markers. Expression levels of proinvasive genes (IL-1α, IL-6, IL-8, and urokinase plasminogen activator [UPA]) were higher in cell lines with a significant CD44+/CD24- population than in other cell lines. Among the CD44+/CD24--positive cell lines, MDA-MB-231 has the unique property of expressing a broad range of genes that favor bone and lung metastasis. Consistent with previous studies in nude mice, cell lines with CD44+/CD24- subpopulation were more invasive than other cell lines. However, only a subset of CD44+/CD24--positive cell lines was able to home and proliferate in lungs. Conclusion Breast cancer cells with CD44+/CD24- subpopulation express higher levels of proinvasive genes and have highly invasive properties. However, this phenotype is not sufficient to predict capacity for pulmonary metastasis.
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    EFFECTS OF RESVERATROL ON PACLITAXEL-SENSITIVE AND –RESISTANT TRIPLE NEGATIVE BREAST CANCER CELLS
    (Office of the Vice Chancellor for Research, 2012-04-13) Sprouse, Alyssa A.; Herbert, Brittney-Shea
    Treatment of drug-resistant cancer cells remains a difficult problem in cancer therapy because most resistant cells can pump out drugs or upregulate other survival pathways to bypass a targeted therapy. The poly-phenol natural compound, resveratrol, has been shown to inhibit cell growth of multiple cancer types, but it is not cytotoxic to normal cells. However, the effects of resveratrol in triple negative breast cancer cells as well as cancers that are resistant to the common cancer drug, paclitaxel, are not well under-stood. In this study, the effects of resveratrol were investigated in the triple negative breast cancer cell line MDA-MB-231 as well as a novel paclitaxel-resistant MDA-MB-231 derived line generated in our laboratory. Both cell lines exhibited a reduction in cell proliferation after resveratrol treatment, with the paclitaxel-resistant cells to a greater extent. In addition, resveratrol decreased the ability of both cell lines to form colonies when plated at low density indicating reduced cell survival capacity. Resveratrol treatment also increased the amount of DNA fragmentation associated with cell death in both cell lines, again with the paclitaxel resistant cells being more sensitive. By protein expression analyses, we observed that in both the parental and resistant cell lines, resveratrol may be acting by through NAD-dependent deacetylase sirtuin (SIRT1) activity by decreasing the expression of the in-hibitor-of-apoptosis protein, survivin, as well as increasing the activator-of-cell death, caspase 7. These data suggest that resveratrol can inhibit prolif-eration and induce cell death in triple negative breast cancer cells, including paclitaxel-resistant cells. In addition, these results provide rationale for the use of resveratrol as an important starting point for the development of a novel anti-cancer agent for drug resistant, aggressive cancers as well as in combination with other anti-cancer drugs without significant toxicity to nor-mal cells.
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    Negative Regulation of Transactivation Function but Not DNA Binding of NF-κB and AP-1 by IκBβ1 in Breast Cancer Cells
    (1999-06-25) Newton, Thomas R.; Patel, Nikhil M.; Bhat-Nakshatri, Poornima; Stauss, Carmen R.; Goulet, Robert J.; Nakshatri, Harikrishna
    The transcription factor NF-κB regulates the expression of genes involved in cancer cell invasion, metastasis, angiogenesis, and resistance to chemotherapy. In normal cells NF-κB is maintained in the cytoplasm by protein-protein interaction with inhibitor IκBs. In contrast, in cancer cells a substantial amount of NF-κB is in the nucleus and constitutively activates target genes. To understand the mechanisms of constitutive NF-κB activation, we have analyzed the function of IκBα and IκBβ in breast cancer cells. In most cases, constitutive NF-κB DNA binding correlated with reduced levels of either IκBα or IκBβ isoforms. Overexpression of IκBα but not IκBβ1 resulted in reduced constitutive DNA binding of NF-κB in MDA-MB-231 cells. Unexpectedly, IκBβ1 overexpression moderately increased 12-O-tetradecanoylphorbol-13-acetate- and interleukin-1-inducible NF-κB DNA binding. 12-O-Tetradecanoylphorbol-13-acetate- and interleukin-1-induced transactivation by NF-κB, however, was lower in IκBβ1-overexpressing cells. Mutants of IκBβ1 lacking the C-terminal casein kinase II phosphorylation sites, which form a stable complex with DNA bound NF-κB without inhibiting its transactivation in other cell types, repressed the transactivation by NF-κB in MDA-MB-231 cells. Consistent with the results of transient transfections, the expression of urokinase plasminogen activator, an NF-κB target gene, was reduced in IκBβ1-overexpressing cells. These results suggest that depending on the cell type, IκBβ1 represses the expression of NF-κB-regulated genes by inhibiting either DNA binding or transactivation function of NF-κB.