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[Role of heterogeneous nuclear ribonucleoprotein A2/B1 protein in the pathogenesis of non-small cell lung cancer].

AbstractOBJECTIVE:
To study the expression of heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNP A2/B1) in non-small cell lung cancer (NSCLC), and the interaction between hnRNP A2/B1 protein and mRNA of DNA repair enzymes O(6)-methylguanine DNA-methyltransferase (MGMT), 8-oxoguanine DNA glycosylase (OGG1), redox factor 1(Ref-1), DNA-dependent protein kinase (including DNA-PKcs and ku).
METHODS:
The expression and distribution of hnRNP A2/B1 were detected by immunohistochemistry and Western blot on 50 NSCLC samples from patients who underwent resection in Zhongshan Hospital. The hnRNP A2/B1 mRNA expression was tested by real-time PCR. Co-immunoprecipitation (co-IP) combined RT-PCR was used to investigate whether hnRNP A2/B1 could be bound with the mRNA of the above mentioned 5 DNA repair enzymes in human lung cancer cell line (HTB-182). Then immunohistochemistry and real-time PCR were used to detect the expression of MGMT in the same group of patients.
RESULTS:
HnRNP A2/B1 protein and mRNA expressions were increased in the NSCLC tissues than that in the corresponding normal lung tissues. HnRNP A2/B1 was expressed predominantly in the nuclei of tumor cells. The positive rate and immunohistochemistry score of hnRNP A2/B1 in tumor tissue were significantly higher than that in normal tissue (P < 0.01). In stage III-IV NSCLC, hnRNP A2/B1 expression was higher than that in stage I-II. There was no significant differences of hnRNP A2/B1 expression among patients of different age, sex, histological type, and smoking history. The results of co-IP combined RT-PCR suggested that hnRNP A2/B1 is bound with MGMT mRNA, and MGMT expression is decreased in tumor tissue of NSCLC.
CONCLUSIONS:
The results of this study show that hnRNP A2/B1 protein and mRNA are highly expressed in NSCLC, and hnRNP A2/B1 is bound with MGMT mRNA, which indicate that it might be one of the mechanisms of hnRNP A2/B1 participating in the pathogenesis of NSCLC.
AuthorsYuan Shi, Ying Chen, Ying-yong Hou, Chun-hua Ji, Qin Hu, Yang Zhou, Jie-akesu Su, Yun-shan Tan
JournalZhonghua zhong liu za zhi [Chinese journal of oncology] (Zhonghua Zhong Liu Za Zhi) Vol. 33 Issue 2 Pg. 110-4 (Feb 2011) ISSN: 0253-3766 [Print] China
PMID21575478 (Publication Type: English Abstract, Journal Article)
Chemical References
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B
  • RNA, Messenger
  • hnRNP A2
  • 8-hydroxyguanine
  • Guanine
  • O-(6)-methylguanine
  • DNA-Activated Protein Kinase
Topics
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung (genetics)
  • DNA-Activated Protein Kinase (metabolism)
  • Guanine (analogs & derivatives)
  • Heterogeneous-Nuclear Ribonucleoprotein Group A-B (genetics, metabolism)
  • Humans
  • Immunohistochemistry
  • Immunoprecipitation
  • Lung (chemistry)
  • Lung Neoplasms (genetics)
  • RNA, Messenger (analysis)
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

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