Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3K/Akt (original) (raw)

Abstract.

The E5 oncoprotein of human papillomavirus (HPV) 16 plays an important role in early cervical carcinogenesis. Vascular endothelial growth factor (VEGF) plays a central role in switching on the angiogenic phenotype during early cervical carcinogenesis. However, the relationship between E5 and VEGF has not previously been examined. To clarify the regulatory role of E5 in VEGF expression, we transferred the E5 gene into various cell types. E5 increased VEGF expression. The addition of epidermal growth factor receptor (EGFR) inhibitor significantly suppressed VEGF expression, demonstrating that E5 stimulates VEGF expression through the activation of EGFR. E5-mediated EGFR activation was accompanied by phosphorylation of Akt and ERK1/2, which are also involved in VEGF expression. Furthermore, the mRNA stability of VEGF was not affected by E5, but VEGF promoter activity could be modulated by inhibitors of the EGFR, MEK-ERK1/2 and PI3K/Akt pathways in E5-expressing cells. Collectively, these novel results suggest that HPV 16 E5 increases VEGF expression by activating EGFR, MEK/ERK1/2 and PI3K/Akt.

Access this article

Log in via an institution

Subscribe and save

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

Author information

Authors and Affiliations

  1. Cancer Research Institute, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea
    S. -H. Kim, Y. -S. Juhnn, S. -W. Park, M. -W. Sung, Y. -J. Bang & Y. -S. Song
  2. Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea
    Y. -S. Juhnn
  3. Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea
    Y. -J. Bang
  4. Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, 28 Yongun-dong, Chongno-gu, Seoul, 110-744, Korea
    M. -W. Sung
  5. Department of Obstetrics and Gynecology, Seoul National University, College of Medicine, 28 Yungun-Dong, Chongno-Ku, Seoul, 110-744, Korea
    S. Kang & Y. -S. Song

Authors

  1. S. -H. Kim
    You can also search for this author inPubMed Google Scholar
  2. Y. -S. Juhnn
    You can also search for this author inPubMed Google Scholar
  3. S. Kang
    You can also search for this author inPubMed Google Scholar
  4. S. -W. Park
    You can also search for this author inPubMed Google Scholar
  5. M. -W. Sung
    You can also search for this author inPubMed Google Scholar
  6. Y. -J. Bang
    You can also search for this author inPubMed Google Scholar
  7. Y. -S. Song
    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence toY. -S. Song.

Additional information

Received 23 November 2005; received after revision 10 January 2006; accepted 9 February 2006

Rights and permissions

About this article

Cite this article

Kim, S.H., Juhnn, Y.S., Kang, S. et al. Human papillomavirus 16 E5 up-regulates the expression of vascular endothelial growth factor through the activation of epidermal growth factor receptor, MEK/ ERK1,2 and PI3K/Akt.Cell. Mol. Life Sci. 63, 930–938 (2006). https://doi.org/10.1007/s00018-005-5561-x

Download citation

Keywords.