title: SHP1-mediated cell cycle redistribution inhibits radiosensitivity of non-small cell lung cancer.
abstract: BACKGROUND
  Radioresistance is the common cause for radiotherapy failure in non-small cell lung cancer (NSCLC), and the degree of radiosensitivity of tumor cells is different during different cell cycle phases. The objective of the present study was to investigate the effects of cell cycle redistribution in the establishment of radioresistance in NSCLC, as well as the signaling pathway of SH2 containing Tyrosine Phosphatase (SHP1).
  
  
  METHODS
  A NSCLC subtype cell line, radioresistant A549 (A549S1), was induced by high-dose hypofractionated ionizing radiations. Radiosensitivity-related parameters, cell cycle distribution and expression of cell cycle-related proteins and SHP1 were investigated. siRNA was designed to down-regulate SHP1expression.
  
  
  RESULTS
  Compared with native A549 cells, the proportion of cells in the S phase was increased, and cells in the G0/G1 phase were consequently decreased, however, the proportion of cells in the G2/M phase did not change in A549S1 cells. Moreover, the expression of SHP1, CDK4 and CylinD1 were significantly increased, while p16 was significantly down-regulated in A549S1 cells compared with native A549 cells. Furthermore, inhibition of SHP1 by siRNA increased the radiosensitivity of A549S1 cells, induced a G0/G1 phase arrest, down-regulated CDK4 and CylinD1expressions, and up-regulated p16 expression.
  
  
  CONCLUSIONS
  SHP1 decreases the radiosensitivity of NSCLC cells through affecting cell cycle distribution. This finding could unravel the molecular mechanism involved in NSCLC radioresistance.
authors.affiliation: Cancer Center of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No, 1227 Jiefang Dadao, Wuhan 430022, China.
authors.forename: Rubo
authors.initials: R
authors.lastname: Cao
authors.forename: Qian
authors.initials: Q
authors.lastname: Ding
authors.forename: Pindong
authors.initials: P
authors.lastname: Li
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Zou
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.forename: Gang
authors.initials: G
authors.lastname: Peng
mesh_terms: D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D005434:Flow Cytometry; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6 / Q000096:biosynthesis / Q000235:genetics*; D034741:RNA, Small Interfering; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; C509249:PTPN6 protein, human; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6