Genomic instability mediated by papillomavirus oncogenes (GIMPO)

Background

The HPV oncoproteins E6 and E7 interact with various host cellular factors and pathways promoting the transformation of the host cell. Most prominent are the interactions of E6 with the tumor suppressive protein p53, and of E7 with the retinoblastoma protein Rb. Both target proteins play important roles in cell cycle regulation, apoptosis pathways and maintenance of genomic stability.

What we do

In the GIMPO project we study the effects of the HPV oncogenes on genomic stability and DNA integrity of the host cells. Therefore, we modified an immortal nearly diploid cancer cell line to express E6 and E7 induced by doxycycline.

Why we do it

Up to now, targeted therapies interfering with the oncogenic activities of E6 and E7 are still missing. The effects of E6 and E7 on genomic integrity have been described in primary keratinocytes and in cervical cancer cell lines, which are either critical for long-term culturing or already chromosomally instable. These limitations can be overcome by using our inducible expression system in nearly diploid cancer cells. Therefore, this system will help us to understand the oncogenic activities of E6 and E7 and might allow the identification of drugable functions.

Key publications

• Thomas LK, Bermejo JL, Vinokurova S, Jensen K, Bierkens M, Steenbergen R, Bergmann M, von Knebel Doeberitz M, Reuschenbach M. Chromosomal gains and losses in human papillomavirus-associated neoplasia of the lower genital tract - a systematic review and meta-analysis. Eur J Cancer. 2014 Jan;50(1):85-98.