| 1. |
- Engström, Wilhelm
(författare)
-
Role of fibroblast growth factors in elicitation of cell responses
- 2014
-
Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 47, s. 3-11
-
Tidskriftsartikel (refereegranskat)abstract
- Fibroblast growth factors (FGFs) are signalling peptides that control important cell processes such as proliferation, differentiation, migration, adhesion and survival. Through binding to different types of receptor on the cell surface, these peptides can have different effects on a target cell, the effect achieved depending on many features. Thus, each of the known FGFs elicits specific biological responses. FGF receptors (FGFR 1-5) initiate diverse intracellular pathways, which in turn lead to a variety of results. FGFs also bind the range of FGFRs with a series of affinities and each type of cells expresses FGFRs in different qualitative and quantitative patterns, which also affect responses. To summarize, cell response to binding of an FGF ligand depends on type of FGF, FGF receptor and target cell, all interacting in concert. This review aims to examine properties of the FGF family and its members receptors. It also aims to summarize features of intracellular signalling and highlight differential effects of the various FGFs in different circumstances.
|
|
| 2. |
|
|
| 3. |
- Fredlund, Jan O, et al.
(författare)
-
Abnormal DNA synthesis in polyamine deficient cells revealed by bromodeoxyuridine-flow cytometry technique
- 1994
-
Ingår i: Cell Proliferation. - : Wiley. - 1365-2184 .- 0960-7722. ; 27:5, s. 243-256
-
Tidskriftsartikel (refereegranskat)abstract
- Chinese hamster ovary cells were seeded in the absence or presence of the polyamine synthesis inhibitor 2-difluoromethylornithine (DFMO). At 1-4 days after seeding, the cells were labelled for 15-120 min with the thymidine analogue bromodeoxyuridine (BrdUrd) and they were then fixed directly after the labelling period. In addition, cells were labelled for 30 min and they were then allowed to progress in BrdUrd-free medium during a defined post-labelling time before fixation. An indirect immunofluorescence technique, using the monoclonal BrdUrd antibody and the intercalating stochiometric DNA stain, propidium iodide, was applied to enable quantification of cellular BrdUrd and DNA contents, respectively, by flow cytometry (FCM). By comparing the mean DNA content of BrdUrd-labelled cells to the mean DNA contents of G(1) and G(2) cells, a relative measure of the position of the BrdUrd-labelled cells was obtained (relative movement). Relative movement data, obtained from control and DFMO-treated cells fixed directly after BrdUrd labelling, indicated that DFMO-treated cells entered S phase at a normal rate, while their progression through S phase was impaired. DNA histograms of BrdUrd-labelled control cells fixed directly after labelling showed that most cells were found in early and late S phase, while DNA histograms of BrdUrd-labelled DFMO-treated cells showed that most cells were in early S phase, indicating a delayed progression through S phase. Analysis of relative movement of cells that were allowed to progress in BrdUrd-free medium after labelling showed that DFMO treatment resulted in a significant lengthening of the DNA synthesis time. Labelling index was significantly higher in DFMO-treated, growth-inhibited cells than in early plateau phase control cells indicating an S phase accumulation in the former cells.
|
|
| 4. |
- Greuel, Selina, et al.
(författare)
-
Effect of inoculum density on human-induced pluripotent stem cell expansion in 3D bioreactors
- 2019
-
Ingår i: Cell Proliferation. - : WILEY. - 0960-7722 .- 1365-2184. ; 52:4
-
Tidskriftsartikel (refereegranskat)abstract
- Objective For optimized expansion of human-induced pluripotent stem cells (hiPSCs) with regards to clinical applications, we investigated the influence of the inoculum density on the expansion procedure in 3D hollow-fibre bioreactors. Materials and Methods Analytical-scale bioreactors with a cell compartment volume of 3 mL or a large-scale bioreactor with a cell compartment volume of 17 mL were used and inoculated with either 10 x 10(6) or 50 x 10(6) hiPSCs. Cells were cultured in bioreactors over 15 days; daily measurements of biochemical parameters were performed. At the end of the experiment, the CellTiter-Blue (R) Assay was used for culture activity evaluation and cell quantification. Also, cell compartment sections were removed for gene expression and immunohistochemistry analysis. Results The results revealed significantly higher values for cell metabolism, cell activity and cell yields when using the higher inoculation number, but also a more distinct differentiation. As large inoculation numbers require cost and time-extensive pre-expansion, low inoculation numbers may be used preferably for long-term expansion of hiPSCs. Expansion of hiPSCs in the large-scale bioreactor led to a successful production of 5.4 x 10(9) hiPSCs, thereby achieving sufficient cell amounts for clinical applications. Conclusions In conclusion, the results show a significant effect of the inoculum density on cell expansion, differentiation and production of hiPSCs, emphasizing the importance of the inoculum density for downstream applications of hiPSCs. Furthermore, the bioreactor technology was successfully applied for controlled and scalable production of hiPSCs for clinical use.
|
|
| 5. |
- Hashemi, M., et al.
(författare)
-
Adenosine and deoxyadenosine induces apoptosis in oestrogen receptor-positive and -negative human breast cancer cells via the intrinsic pathway
- 2005
-
Ingår i: Cell Proliferation. - : Wiley-Blackwell. - 0960-7722 .- 1365-2184. ; 38:5, s. 269-285
-
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.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Islam, Quamrul, 1952-, et al.
(författare)
-
Generation of somatic cell hybrids for the production of biologically active factors that stimulate proliferation of other cells
- 2007
-
Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 40:1, s. 91-105
-
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.
|
|
| 9. |
|
|
| 10. |
- Johansson, Maria C, et al.
(författare)
-
Comparison of mathematical formulas used for estimation of DNA synthesis time of bromodeoxyuridine-labelled cell populations with different proliferative characteristics
- 1996
-
Ingår i: Cell Proliferation. - : Wiley. - 1365-2184 .- 0960-7722. ; 29:10, s. 525-538
-
Tidskriftsartikel (refereegranskat)abstract
- Growth kinetic data of human tumours, obtained by flow cytometric analysis of cells labelled with bromodeoxyuridine (BrdUrd) might provide prognostic information and allow prediction of response to radio- and chemotherapy. However, the theoretical models applied for calculation of growth kinetic data are not fully evaluated. The purpose of this study was to investigate the dependence of the estimation of DNA synthesis time (Ts) on sampling time after BrdUrd labelling, using four different mathematical formulas (Begg et al., White & Meistrich, White et al. and Johansson et al.) which have been developed for the evaluation of flow cytometry-derived data of BrdUrd-labelled cells. In addition, we have investigated the influence of the growth kinetic properties of the cell populations using two cultured cell lines (one slow and one fast growing), and two hetero-transplanted human tumours. The dependence of the estimation of Ts on sampling time was more or less pronounced, depending on the cell population examined and on the formula used. In the fast growing cell line, the estimates of Ts did not vary significantly with sampling time when using the formulas by White et al., whereas in the slow growing cell line, the estimates of Ts did not show any significant dependence on sampling time when using the formula by Johansson et al. In the tumours, the estimation of Ts depended on sampling time with all formulas used, although to different degrees. In one of the tumours, this was mainly caused by the influence of mouse cells, as we demonstrate. Our results indicate that the proliferative characteristics of a cell population should be taken into consideration when choosing a mathematical formula in order to attain Ts values that are independent of sampling time.
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
- Maddika, Subbareddy, et al.
(författare)
-
Akt is transferred to the nucleus of cells treated with apoptin, and it participates in apoptin-induced cell death
- 2007
-
Ingår i: Cell Proliferation. - : Wiley-Blackwell. - 0960-7722 .- 1365-2184. ; 40:6, s. 835-848
-
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.
|
|
| 14. |
|
|
| 15. |
- Nordin, Matilda, et al.
(författare)
-
Epigenetic regulation of the Igf2/H19 gene cluster
- 2014
-
Ingår i: Cell Proliferation. - : Wiley. - 0960-7722 .- 1365-2184. ; 47, s. 189-199
-
Tidskriftsartikel (refereegranskat)abstract
- Igf2 (insulin-like growth factor 2) and H19 genes are imprinted in mammals; they are expressed unevenly from the two parental alleles. Igf2 is a growth factor expressed in most normal tissues, solely from the paternal allele. H19 gene is transcribed (but not translated to a protein) from the maternal allele. Igf2 protein is a growth factor particularly important during pregnancy, where it promotes both foetal and placental growth and also nutrient transfer from mother to offspring via the placenta. This article reviews epigenetic regulation of the Igf2/H19 gene-cluster that leads to parent-specific expression, with current models including parental allele-specific DNA methylation and chromatin modifications, DNA-binding of insulator proteins (CTCFs) and three-dimensional partitioning of DNA in the nucleus. It is emphasized that key genomic features are conserved among mammals and have been functionally tested in mouse. The enhancer competition model', the boundary model' and the chromatin-loop model' are three models based on differential methylation as the epigenetic mark responsible for the imprinted expression pattern. Pathways are discussed that can account for allelic methylation differences; there is a recent study that contradicts the previously accepted fact that biallelic expression is accompanied with loss of differential methylation pattern.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Zander, Linda, 1976, et al.
(författare)
-
Identification of genes deregulated in a Burkitt´s lymphoma cell line when adapted for
- 2008
-
Ingår i: Cell Proliferation. - : Wiley. - 1365-2184 .- 0960-7722. ; 41:1, s. 136-155
-
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.
|
|
| 21. |
- Zhang, Juqing, et al.
(författare)
-
Super enhancers-Functional cores under the 3D genome
- 2021
-
Ingår i: Cell Proliferation. - : John Wiley & Sons. - 0960-7722 .- 1365-2184. ; 54:2
-
Forskningsöversikt (refereegranskat)abstract
- Complex biochemical reactions take place in the nucleus all the time. Transcription machines must follow the rules. The chromatin state, especially the three-dimensional structure of the genome, plays an important role in gene regulation and expression. The super enhancers are important for defining cell identity in mammalian developmental processes and human diseases. It has been shown that the major components of transcriptional activation complexes are recruited by super enhancer to form phase-separated condensates. We summarize the current knowledge about super enhancer in the 3D genome. Furthermore, a new related transcriptional regulation model from super enhancer is outlined to explain its role in the mammalian cell progress.
|
|
| 22. |
|
|
