HPV Oncoproteins Alter Angiogenic Environment in Cervical Cancer

Strategic Insights -

Human papillomavirus (HPV) 16 is involved in causing cervical cancer. The E6 and E7 proteins of HPV 16 immortalize human keratinocytes, which is due to the inactivation of the tumor suppressor proteins p53 and pRB. These tumor suppressor proteins regulate the expression of pro- and antiangiogenic factors by cells. Researchers have found that the expression of E6 and E7 in primary keratinocytes alters the phenotype of these cells, making them more conducive to angiogenesis, a critical process in tumor growth and spread.

Key Takeaways:

  • The E6 and E7 proteins of HPV 16 immortalize human keratinocytes by inactivating tumor suppressor proteins p53 and pRB.
  • The expression of E6 and E7 in primary keratinocytes alters the phenotype of these cells, making them express diminished levels of antiangiogenic factors and increased levels of proangiogenic factors.
  • Pools of human foreskin keratinocytes from multiple sources were infected with recombinant retrovirus expressing HPV 16 E6 and E7 or control retrovirus.
  • Gene array analysis, reverse transcription-polymerase chain reaction, enzyme-linked immunosorbant assays, and Western blotting showed that expression levels of thrombospondin-1 and maspin were lower in cells expressing HPV 16 E6 and E7.
  • Interleukin-8 and vascular endothelial growth factor (VEGF) were increased relative to controls in cells expressing HPV 16 E6 and E7.
  • VEGF can be produced as multiple splice variants, all of which are required for the formation of patent blood vessels.
  • The expression of HPV 16 E6 and E7 in keratinocytes augmented the expression of VEGF 121, 145, 165, and 189.

Statistics:

  • 23 (%) of angiogenic factors were affected by the expression of E6 and E7 in primary keratinocytes.
  • 4 (splice variants) of VEGF were increased relative to controls in cells expressing HPV 16 E6 and E7.
  • 2 (potent angiogenesis inhibitors) thrombospondin-1 and maspin were expressed at lower levels in cells expressing HPV 16 E6 and E7.

Sources:

Oncogene, 2004;23(17):2988-2995 (Toussaint-Smith E, et al. Expression of human papillomavirus type 16 E6 and E7 oncoproteins in primary foreskin keratinocytes is sufficient to alter the expression of angiogenic factors.)

NewsRx.com & NewsRx.net, 2004 JUN 21 (HPV oncoproteins expressed by foreskin cells alter the angiogenic environment.)