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Upregulated Expression of Periostin by Hypoxia in Non-small-cell Lung Cancer Cells Promotes Cell Survival Via the Akt/PKB Pathway

Author: RuanKai
Tutor: OuYangGaoLiang
School: Xiamen University
Course: Cell Biology
Keywords: Periostin Hypoxia Tumor microenvironment Cell survival Akt
CLC: R734.2
Type: Master's thesis
Year: 2009
Downloads: 157
Quote: 0
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Abstract


Human tumorigenesis is a complex multi-step process, due to increased genomic instability, resulting in normal tissue at a series of genetic variation, epigenetic changes and somatic mutation. Interactions between the components of the tumor cells by neighboring host a tumor - host interface microenvironment, regulating a variety of intracellular signaling pathways to coordinate the adaptive growth of cells respond to different micro-environments. Important cause of the tumor microenvironment because of the unique physiological characteristics of tumor proliferation, invasion, migration, adhesion ability and the formation of new blood vessels have a major impact, the tumor is deteriorating and metastasis. Hypoxia as one of the salient features of which, in cell proliferation, survival, angiogenesis, plays an important role in immune surveillance, tumor cell metabolism and tumor invasion and metastasis. Periostin protein as a family of extracellular matrix components Matricellular Proteins in a variety of human cancers, over-expression may be involved in mediating cell-matrix interactions, thereby promoting tumor cell adhesion, migration, and survival. Our previous cooperation studies have shown that mouse recombinant Periostin protein can promote metastasis of colon cancer cells by enhancing the ability of cell survival, growth. Periostin protein in lung cancer cells under hypoxic conditions has the same role, is not yet clear. In this article, we study in non-small cell lung cancer A549 cells, using the the chemical inducer CoCl 2 and DFO processing simulation tumor microenvironment hypoxia by Western blot, RNA interference, apoptosis detection kit and Hoechst staining technology, research Periostin protein in non-small cell lung cancer cell survival under environmental stress conditions and its role in the molecular mechanism. The results showed that hypoxia induced human non-small cell lung cancer A549 cells Periostin protein highly expressed, and the effect is regulated by hypoxia-inducible growth factor TGF-α and bFGF. In addition, it also found Periostin protein expression RTK/PI3-K signaling pathway is activated, TGF-α and bFGF, Periostin protein can be further promoted through the activation of Akt / PKB signaling pathway A549 cell survival under hypoxic conditions. Therefore, the study Periostin protein in to promote molecular mechanisms of tumor cell survival under hypoxic conditions, there will be conducive to the Periostin understanding of the tumor microenvironment under stress conditions as a new kind of antagonistic gene function, and may also be of non-small cell lung cancer detection and treatment provide a new target.

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CLC: > Medicine, health > Oncology > Respiratory system tumors > Lung tumors
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