Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer

Ya W. Cheng, Huei Lee, Ming Y. Shiau, Tzu Chin Wu, Tsung Teng Huang, Yih Hsin Chang

Research output: Contribution to journalArticle

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Abstract

Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis. Experimental Design: IL-6 and Mcl-1 expressions were investigated in 79 tumor tissues from lung cancer patients by immunohitochemistry. Secreting IL-6 levels and Mcl-1 expressions were examined by ELISA and Western blot, respectively, in HPV 16/18 E6- and E7-transfected A549 human lung cancer cells, as well as in the HPV16-infected TL-1 lung cancer cells established from lung cancer patients. Results: Lung tumors (70.9% and 57.0%) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P <0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P - 0.014 and P - 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells. Phosphatidylinositol-3-OH kinase pathway was the major pathway contributing to the up-regulation of Mcl-1 by IL-6 in HPV-infected lung cancer cells. Conclusions: The up-regulating effects of HPV 16/18 E6 and E7 to IL-6 and Mcl-1 expressions were observed in E6- and E7-transfected A549 cells and in HPV16-infected TL-1 cells, mainly through the phosphatidylinositol-3-OH kinase pathway. The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1.

Original languageEnglish
Pages (from-to)4705-4712
Number of pages8
JournalClinical Cancer Research
Volume14
Issue number15
DOIs
Publication statusPublished - Aug 1 2008
Externally publishedYes

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Human papillomavirus 18
Human papillomavirus 16
Non-Small Cell Lung Carcinoma
Interleukin-6
Up-Regulation
Lung Neoplasms
Papillomavirus Infections
Phosphatidylinositol 3-Kinases
Lung
Carcinogenesis
Infection
Neoplasms
Research Design
Western Blotting
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer. / Cheng, Ya W.; Lee, Huei; Shiau, Ming Y.; Wu, Tzu Chin; Huang, Tsung Teng; Chang, Yih Hsin.

In: Clinical Cancer Research, Vol. 14, No. 15, 01.08.2008, p. 4705-4712.

Research output: Contribution to journalArticle

Cheng, Ya W. ; Lee, Huei ; Shiau, Ming Y. ; Wu, Tzu Chin ; Huang, Tsung Teng ; Chang, Yih Hsin. / Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer. In: Clinical Cancer Research. 2008 ; Vol. 14, No. 15. pp. 4705-4712.
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abstract = "Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis. Experimental Design: IL-6 and Mcl-1 expressions were investigated in 79 tumor tissues from lung cancer patients by immunohitochemistry. Secreting IL-6 levels and Mcl-1 expressions were examined by ELISA and Western blot, respectively, in HPV 16/18 E6- and E7-transfected A549 human lung cancer cells, as well as in the HPV16-infected TL-1 lung cancer cells established from lung cancer patients. Results: Lung tumors (70.9{\%} and 57.0{\%}) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P <0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P - 0.014 and P - 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells. Phosphatidylinositol-3-OH kinase pathway was the major pathway contributing to the up-regulation of Mcl-1 by IL-6 in HPV-infected lung cancer cells. Conclusions: The up-regulating effects of HPV 16/18 E6 and E7 to IL-6 and Mcl-1 expressions were observed in E6- and E7-transfected A549 cells and in HPV16-infected TL-1 cells, mainly through the phosphatidylinositol-3-OH kinase pathway. The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1.",
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T1 - Human papillomavirus type 16/18 up-regulates the expression of interleukin-6 and antiapoptotic Mcl-1 in non-small cell lung cancer

AU - Cheng, Ya W.

AU - Lee, Huei

AU - Shiau, Ming Y.

AU - Wu, Tzu Chin

AU - Huang, Tsung Teng

AU - Chang, Yih Hsin

PY - 2008/8/1

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AB - Human papillomavirus (HPV) 16/18 infection is reported to be associated with nonsmoking Taiwanese female lung cancer. In this study, we attempted to further reveal the association between HPV infection with Mcl-1 and interleukin (IL)-6 expressions and to elucidate the roles of HPV infection in lung tumorigenesis. Experimental Design: IL-6 and Mcl-1 expressions were investigated in 79 tumor tissues from lung cancer patients by immunohitochemistry. Secreting IL-6 levels and Mcl-1 expressions were examined by ELISA and Western blot, respectively, in HPV 16/18 E6- and E7-transfected A549 human lung cancer cells, as well as in the HPV16-infected TL-1 lung cancer cells established from lung cancer patients. Results: Lung tumors (70.9% and 57.0%) had positive IL-6 and Mcl-1 immunostainings, respectively. Significant correlation between IL-6 and Mcl-1 expression were observed (P <0.0001). Both IL-6 and Mcl-1 expression were significantly associated with HPV 16/18 infection (P - 0.014 and P - 0.004, respectively). IL-6 and Mcl-1 protein levels were not only elevated in HPV 16/18 E6- and E7-transfected A549 cells but also in TL-1 cells. Phosphatidylinositol-3-OH kinase pathway was the major pathway contributing to the up-regulation of Mcl-1 by IL-6 in HPV-infected lung cancer cells. Conclusions: The up-regulating effects of HPV 16/18 E6 and E7 to IL-6 and Mcl-1 expressions were observed in E6- and E7-transfected A549 cells and in HPV16-infected TL-1 cells, mainly through the phosphatidylinositol-3-OH kinase pathway. The involvement of HPV infection in lung tumorigenesis may be partly through a concomitant increased expression of autocrine and/or paracrine IL-6 and the downstream Mcl-1.

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