| 1. |
- Hashemi, M., et al.
(författare)
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Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway
- 2005
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Ingår i: Cell Proliferation. - : Wiley-Blackwell. - 0960-7722 .- 1365-2184. ; 38:5, s. 269-285
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Tidskriftsartikel (refereegranskat)abstract
- In this study we have examined the cytotoxic effects of different concentrations of adenosine (Ado) and deoxyadenosine (dAdo) on human breast cancer cell lines. Ado and dAdo alone had little effect on cell cytotoxicity. However, in the presence of adenosine deaminase (ADA) inhibitor, EHNA, adenosine and deoxyadenosine led to significant growth inhibition of cells of the lines tested. Ado/EHNA and dAdo/EHNA-induced cell death was significantly inhibited by NBTI, an inhibitor of nucleoside transport, and 5'-amino-5'-deoxyadenosine, an inhibitor of adenosine kinase, but the effects were not affected by 8-phenyltheophylline, a broad inhibitor of adenosine receptors. The Ado/EHNA combination brought about morphological changes consistent with apoptosis. Caspase-9 activation was observed in MCF-7 and MDA-MB468 human breast cancer cell lines on treatment with Ado/EHNA or dAdo/EHNA, but, as expected, caspase-3 activation was only observed in MDA-MB468 cells. The results of the study, thus, suggest that extracellular adenosine and deoxyadenosine induce apoptosis in both oestrogen receptor-positive (MCF-7) and also oestrogen receptor-negative (MDA-MB468) human breast cancer cells by its uptake into the cells and conversion to AMP (dAMP) followed by activation of nucleoside kinase, and finally by the activation of the mitochondrial/intrinsic apoptotic pathway.
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| 2. |
- Islam, Quamrul, 1952-, et al.
(författare)
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Generation of somatic cell hybrids for the production of biologically active factors that stimulate proliferation of other cells
- 2007
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Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 40:1, s. 91-105
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Some normal somatic cells in culture divide a limited number of times before entering a non-dividing state called replicative senescence and fusion of normal cells with immortal cells claimed to produce hybrid cells of limited proliferation. We reinvestigated the proliferative capacity of hybrid cells between normal cell and immortal cell. Materials and Methods: Normal pig fibroblast cells and cells of immortal mouse fibroblast cell line F7, a derivative of GM05267, were fused by polyethylene glycol treatment and subsequently the fused cells were cultured in a selective medium containing hypoxanthine-aminopterin-thymidine in order to enrich the hybrid cells. The hybrid cells were then monitored for chromosome content and proliferation. Results: Cytogenetic analysis revealed that the hybrid cells contained polyploidy chromosomes derived from normal pig fibroblasts. These hybrid cells exhibit no sign of replicative senescence after more than 190 population doublings in vitro. Instead, these hybrid cells have an accelerated growth and proliferate even in the complete absence of glutamine. In addition, these hybrids produce biologically active factors in the conditioned media, which not only can accelerate their own proliferation but also can reinitiate mitotic activity in the senescent-like normal fibroblast cells. Conclusions: Our results question the validity of cellular senescence as a dominant trait. Additionally, the generation of hybrid cells using the specific mouse cell line can be applied to the generation of hybrids with other normal cell types and can be used to produce tissue-specific growth-factor(s) to extend the lifespan and/or improve the proliferation of various normal cells, including adult stem cells. © 2007 The Authors.
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| 3. |
- Maddika, Subbareddy, et al.
(författare)
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Akt is transferred to the nucleus of cells treated with apoptin, and it participates in apoptin-induced cell death
- 2007
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Ingår i: Cell Proliferation. - : Wiley-Blackwell. - 0960-7722 .- 1365-2184. ; 40:6, s. 835-848
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Tidskriftsartikel (refereegranskat)abstract
- Abstract. Objectives: The phosphatidylinositol 3-kinase (PI3-K)/Akt pathway is well known for the regulation of cell survival, proliferation, and some metabolic routes. Meterials and Methods: In this study, we document a novel role for the PI3-K/Akt pathway during cell death induced by apoptin, a tumour-selective inducer of apoptosis. Results: We show for the first time that apoptin interacts with the p85 regulatory subunit, leading to constitutive activation of PI3-K. The inhibition of PI3-K activation either by chemical inhibitors or by genetic approaches severely impairs cell death induced by apoptin. Downstream of PI3-K, Akt is activated and translocated to the nucleus together with apoptin. Direct interaction between apoptin and Akt is documented. Co-expression of nuclear Akt significantly potentiates cell death induced by apoptin. Thus, apoptin-facilitated nuclear Akt, in contrast to when in its cytoplasmic pool, appears to be a positive regulator, rather than repressor of apoptosis. Conclusions: Our observations indicate that PI3-K/Akt pathways have a dual role in both survival and cell death processes depending on the stimulus. Nuclear Akt acts as apoptosis stimulator rather than as a repressor, as it likely gains access to a new set of substrates in the nucleus. The implicated link between survival and cell death pathways during apoptosis opens new pharmacological opportunities to modulate apoptosis in cancer, for example through the manipulation of Akt's cellular localization.
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| 4. |
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| 5. |
- Zander, Linda, 1976, et al.
(författare)
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Identification of genes deregulated in a Burkitt´s lymphoma cell line when adapted for
- 2008
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Ingår i: Cell Proliferation. - : Wiley. - 1365-2184 .- 0960-7722. ; 41:1, s. 136-155
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Serum is usually added to growth media when mammalian cells are cultured in vitro to supply the cells with growth factors, hormones, nutrients and trace elements. Defined proteins and metal ions, such as insulin, growth factors, transferrin and sodium selenite, are sometimes also included and can in some cases substitute serum components. How adaptation to serum free media influences cells has not been studied in detail. Materials and Methods: We have adapted the Burkitt's lymphoma line Ramos to a serum-free medium that supports long-term survival and studied gene expression changes that occurred during the adaptation process. Results and Conclusions: The adaptation process was characterized by initial cell population growth arrest, and after that extensive cell death, followed by proliferation and long-term survival of clonal cultures. Proliferation and cell cycle progression of the serum-free cultures closely mimicked that of serum-dependent cells. Affymetrix micro-array technology was used to identify gene expression alterations that had occurred during the adaptation. Most changes were subtle, but frequently the genes with altered expression were involved in basal cellular functions such as cell division, cell cycle regulation, apoptosis and cell signalling. Some alterations were restored when the cells were transferred back to serum-containing medium, indicating that expression of these genes was controlled by components in serum. Others were not, and may represent changes that were selected during the adaptation process. Among these were, for example, several genes within the Wnt signalling pathway.
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