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- Maurer, Matthew, et al.
(author)
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3-Phosphoinositide-dependent kinase 1 potentiates upstream lesions on the phosphatidylinositol 3-kinase pathway in breast carcinoma
- 2009
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In: Cancer Research. - 1538-7445. ; 69:15, s. 306-6299
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Journal article (peer-reviewed)abstract
- Lesions of ERBB2, PTEN, and PIK3CA activate the phosphatidylinositol 3-kinase (PI3K) pathway during cancer development by increasing levels of phosphatidylinositol-3,4,5-triphosphate (PIP(3)). 3-Phosphoinositide-dependent kinase 1 (PDK1) is the first node of the PI3K signal output and is required for activation of AKT. PIP(3) recruits PDK1 and AKT to the cell membrane through interactions with their pleckstrin homology domains, allowing PDK1 to activate AKT by phosphorylating it at residue threonine-308. We show that total PDK1 protein and mRNA were overexpressed in a majority of human breast cancers and that 21% of tumors had five or more copies of the gene encoding PDK1, PDPK1. We found that increased PDPK1 copy number was associated with upstream pathway lesions (ERBB2 amplification, PTEN loss, or PIK3CA mutation), as well as patient survival. Examination of an independent set of breast cancers and tumor cell lines derived from multiple forms of human cancers also found increased PDK1 protein levels associated with such upstream pathway lesions. In human mammary cells, PDK1 enhanced the ability of upstream lesions to signal to AKT, stimulate cell growth and migration, and rendered cells more resistant to PDK1 and PI3K inhibition. After orthotopic transplantation, PDK1 overexpression was not oncogenic but dramatically enhanced the ability of ERBB2 to form tumors. Our studies argue that PDK1 overexpression and increased PDPK1 copy number are common occurrences in cancer that potentiate the oncogenic effect of upstream lesions on the PI3K pathway. Therefore, we conclude that alteration of PDK1 is a critical component of oncogenic PI3K signaling in breast cancer.
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| 2. |
- Zhao, Yuli, et al.
(author)
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Relationships between individual small tree canopy structure and rainfall interception
- 2014
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Conference paper (other academic/artistic)abstract
- Among the layers of a plant community, the canopy has the most important hydrological function in water circulation. Understanding the canopy’s inner structure and its relationship to water transport is fundamental for the functional mechanisms of the vegetation canopy. Using an artificial rainfall simulator to supply three levels of rainfall intensity, the interception of rainfall by the canopy was measured to study the characteristics of individual trees using different rainfall conditions and structural parameters. The study was done for four small native tree species: Platycladus orientalis, Pinus tabulaeformis, Quercus variabilis and Acer elegantulum. The resulting variations in the process of canopy interception could be divided into periods of increasing, slightly decreasing in some species, and stable levels of interception. In addition, duration of the initial period of increasing interception shortened as rainfall intensity increased. When rainfall was less intense, the percentage of gross rainfall intercepted by P. orientalis, P. tabulaeformis and A. elegantulum canopy layers was in the order mid > upper > lower canopy, while for Q. variabilis the sequence was upper > mid > lower canopy. These sequences indicate that canopy superstructure was more important than canopy substructure regarding the ability of the canopy to intercept precipitation and thus prevent soil erosion. Furthermore, it was found that exponential and logarithmic functions could be used to describe the relationship between interception of coniferous and deciduous species, respectively, and their own canopy body types. This study provided preliminary criteria for determining the optimal crown type for rainfall interception.
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