IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma

Wen Wei Sung, Yao Chen Wang, Po Lin Lin, Ya Wen Cheng, Chih Yi Chen, Tzu Chin Wu, Huei Lee

Research output: Contribution to journalArticle

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Abstract

Purpose: Interleukin-10 (IL-10) determines virus persistent infection and promotes viral-Associated tumor progression via tumor immune escape. However, the role of IL-10 in tumor progression and prognosis in lung adenocarcinoma remains controversial. Experimental Design: To investigate how IL-10 is regulated by HPV E6, IL-10 promoter was constructed to understand which transcriptional factor could be responsible for its transcription. To verify which molecule could be responsible for IL-10-mediated soft agar growth and invasion capability, PCR array and mechanistic strategies were conducted. IL-10 and CIP2A mRNA levels in lung tumors from patients with lung cancer were determined by real-time reverse transcription PCR. The prognostic value of both molecules on survival was estimated by Cox regression model. Results: Mechanistic studies showed that IL-10 protein and mRNA expression was decreased in E6 knockdown TL1 cells and increased in E6- overexpressing TL4 cells. In addition, IL-10 transcription was predominantly regulated by E6-mediated phosphorylation of cAMP response element-binding protein (CREB) and C/enhancer-binding protein b (C/EBPb) via phosphoinositide 3-kinase (PI3K) signaling pathway. IL-10-mediated tumor aggressiveness in vitro and in vivo occurs through increased CIP2A expression via PI3K signaling pathway. Among patients, IL-10 mRNA expression in lung tumors was positively correlated with CIP2A mRNA expression. Cox-regression analysis showed that IL-10 and CIP2A mRNA levels may independently predict survival in patients with lung adenocarcinoma, especially in patients with E6-positive tumors. Conclusion: IL-10 production from lung tumors and immune cells promotes lung adenocarcinoma aggressiveness and patients with poor survival. We thus suggest that PI3K inhibitor combined with chemotherapy may potentially enhance tumor regression and improve patients' outcome and life quality.

Original languageEnglish
Pages (from-to)4092-4103
Number of pages12
JournalClinical Cancer Research
Volume19
Issue number15
DOIs
Publication statusPublished - Aug 1 2013

Fingerprint

Interleukin-10
Up-Regulation
Neoplasms
1-Phosphatidylinositol 4-Kinase
Messenger RNA
Lung
Survival
Adenocarcinoma of lung
Tumor Escape
Cyclic AMP Response Element-Binding Protein
Polymerase Chain Reaction
Virus Diseases
Protein C
Proportional Hazards Models
Reverse Transcription
Agar
Lung Neoplasms
Carrier Proteins
Research Design
Regression Analysis

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Sung, W. W., Wang, Y. C., Lin, P. L., Cheng, Y. W., Chen, C. Y., Wu, T. C., & Lee, H. (2013). IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma. Clinical Cancer Research, 19(15), 4092-4103. https://doi.org/10.1158/1078-0432.CCR-12-3439

IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma. / Sung, Wen Wei; Wang, Yao Chen; Lin, Po Lin; Cheng, Ya Wen; Chen, Chih Yi; Wu, Tzu Chin; Lee, Huei.

In: Clinical Cancer Research, Vol. 19, No. 15, 01.08.2013, p. 4092-4103.

Research output: Contribution to journalArticle

Sung, Wen Wei ; Wang, Yao Chen ; Lin, Po Lin ; Cheng, Ya Wen ; Chen, Chih Yi ; Wu, Tzu Chin ; Lee, Huei. / IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma. In: Clinical Cancer Research. 2013 ; Vol. 19, No. 15. pp. 4092-4103.
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abstract = "Purpose: Interleukin-10 (IL-10) determines virus persistent infection and promotes viral-Associated tumor progression via tumor immune escape. However, the role of IL-10 in tumor progression and prognosis in lung adenocarcinoma remains controversial. Experimental Design: To investigate how IL-10 is regulated by HPV E6, IL-10 promoter was constructed to understand which transcriptional factor could be responsible for its transcription. To verify which molecule could be responsible for IL-10-mediated soft agar growth and invasion capability, PCR array and mechanistic strategies were conducted. IL-10 and CIP2A mRNA levels in lung tumors from patients with lung cancer were determined by real-time reverse transcription PCR. The prognostic value of both molecules on survival was estimated by Cox regression model. Results: Mechanistic studies showed that IL-10 protein and mRNA expression was decreased in E6 knockdown TL1 cells and increased in E6- overexpressing TL4 cells. In addition, IL-10 transcription was predominantly regulated by E6-mediated phosphorylation of cAMP response element-binding protein (CREB) and C/enhancer-binding protein b (C/EBPb) via phosphoinositide 3-kinase (PI3K) signaling pathway. IL-10-mediated tumor aggressiveness in vitro and in vivo occurs through increased CIP2A expression via PI3K signaling pathway. Among patients, IL-10 mRNA expression in lung tumors was positively correlated with CIP2A mRNA expression. Cox-regression analysis showed that IL-10 and CIP2A mRNA levels may independently predict survival in patients with lung adenocarcinoma, especially in patients with E6-positive tumors. Conclusion: IL-10 production from lung tumors and immune cells promotes lung adenocarcinoma aggressiveness and patients with poor survival. We thus suggest that PI3K inhibitor combined with chemotherapy may potentially enhance tumor regression and improve patients' outcome and life quality.",
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AB - Purpose: Interleukin-10 (IL-10) determines virus persistent infection and promotes viral-Associated tumor progression via tumor immune escape. However, the role of IL-10 in tumor progression and prognosis in lung adenocarcinoma remains controversial. Experimental Design: To investigate how IL-10 is regulated by HPV E6, IL-10 promoter was constructed to understand which transcriptional factor could be responsible for its transcription. To verify which molecule could be responsible for IL-10-mediated soft agar growth and invasion capability, PCR array and mechanistic strategies were conducted. IL-10 and CIP2A mRNA levels in lung tumors from patients with lung cancer were determined by real-time reverse transcription PCR. The prognostic value of both molecules on survival was estimated by Cox regression model. Results: Mechanistic studies showed that IL-10 protein and mRNA expression was decreased in E6 knockdown TL1 cells and increased in E6- overexpressing TL4 cells. In addition, IL-10 transcription was predominantly regulated by E6-mediated phosphorylation of cAMP response element-binding protein (CREB) and C/enhancer-binding protein b (C/EBPb) via phosphoinositide 3-kinase (PI3K) signaling pathway. IL-10-mediated tumor aggressiveness in vitro and in vivo occurs through increased CIP2A expression via PI3K signaling pathway. Among patients, IL-10 mRNA expression in lung tumors was positively correlated with CIP2A mRNA expression. Cox-regression analysis showed that IL-10 and CIP2A mRNA levels may independently predict survival in patients with lung adenocarcinoma, especially in patients with E6-positive tumors. Conclusion: IL-10 production from lung tumors and immune cells promotes lung adenocarcinoma aggressiveness and patients with poor survival. We thus suggest that PI3K inhibitor combined with chemotherapy may potentially enhance tumor regression and improve patients' outcome and life quality.

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