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Search: WFRF:(Perks C M)

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1.
  • Joosen, R.V.L., et al. (author)
  • Correlating gene expression to physiological parameters and environmental conditions during cold acclimation of Pinus sylvestris, identification of molecular markers using cDNA microarrays
  • 2006
  • In: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 26:10, s. 1297-1313
  • Journal article (peer-reviewed)abstract
    • Scots pine (Pinus sylvestris L.) seedlings were grown under different conditions (three field locations, two seasons and two climate room regimes), and then analyzed for freezing tolerance of shoots and roots and for transcript abundance in apical buds based on a cDNA microarray containing about 1500 expressed sequence tags (ESTs) from buds of cold-treated Scots pine seedlings. In a climate room providing long daily photoperiods and high temperatures, seedlings did not develop freezing tolerance, whereas seedlings in a climate room set to provide declining temperatures and day lengths developed moderate freezing tolerance. Control seedlings grown outside under field conditions developed full freezing tolerance. Differences in physiological behavior of the different seedling groups, combined with molecular analysis, allowed identification of a large group of genes, expression of which changed during the development of freezing tolerance. Transcript abundance of several of these genes was highly correlated with freezing tolerance in seedlings differing in provenance, field location or age, making them excellent candidate marker genes for molecular tests for freezing tolerance.
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2.
  • Hale, L J, et al. (author)
  • Insulin-like growth factor-II is produced by, signals to and is an important survival factor for the mature podocyte in man and mouse
  • 2013
  • In: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 230:1, s. 95-106
  • Journal article (peer-reviewed)abstract
    • Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro-survival mechanisms are critically important. Insulin-like growth factor-II (IGF-II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF-II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF-II; it signals to this cell via the IGF-I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF-II transgenic mouse that produces approximately 60% of IGF-II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF-II in the mature podocyte for glomerular health across mammalian species.
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3.
  • Perks, C. M., et al. (author)
  • IGF-II and IGFBP-2 differentially regulate PTEN in human breast cancer cells
  • 2007
  • In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 26:40, s. 5966-5972
  • Journal article (peer-reviewed)abstract
    • The dual-function phosphatase and tensin homolog deleted on chromosome 10 ( PTEN) is the second most frequently mutated gene in human cancers. PTEN counteracts the functions of many growth factors, the most prevalent of which is insulin-like growth factor II ( IGF-II). PTEN expression is stimulated by IGF-II forming a feedback loop. Investigating IGF-binding protein ( IGFBP) modulation of IGF-II actions on MCF-7 breast cancer cells, we found that IGFBP-2 also regulates PTEN. The MCF-7 cells were not responsive to high doses of IGF-II due to induction of PTEN, which was not observed with an IGF-II-analog that does not bind to IGFBPs or in the presence of an inhibitor that prevents IGFs associating with IGFBPs. These cells predominantly produce IGFBP-2: blocking IGFBP-2 with a specific antibody, or preventing IGFBP-2 binding to integrins, restored the induction of PTEN and the cells were non-responsive to high doses of the IGF-II-analog. Our. findings indicate that breast cancer cells do not respond to high doses of IGF-II due to induction of PTEN, but IGFBP-2, when free from IGF-II can suppress PTEN. Levels of IGFBP-2 are elevated frequently in human tumors: its ability to regulate PTEN could have important implications in relation to therapeutic strategies targeting growth factor pathways.
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