INTEGRATION OF HUMAN PAPILLOMAVIRUS TYPE-16 DNA INTO THE HUMAN GENOMELEADS TO INCREASED STABILITY OF E6 AND E7 MESSENGER-RNAS - IMPLICATIONS FOR CERVICAL CARCINOGENESIS

In many cervical cancers, human papillomavirus type 16 (HPV-16) DNA ge nomes are found to be integrated into the host chromosome. In this stu dy, we demonstrate that integration of HPV-16 DNA leads to increased s teady-state levels of mRNAs encoding the viral oncogenes E6 and E7. Th is increase is shown to result, at least in part, from an increased st ability of E6 and E7 mRNAs that arise specifically from those integrat ed viral genomes disrupted in the 3' untranslated region of the viral early region. Further, we demonstrate that the A+U-rich element within this viral early 3' untranslated region confers instability on a hete rologous mRNA. We conclude that integration of HPV-16 DNA, as occurs i n cervical cancers, can result in the increased expression of the vira l E6 and E7 oncogenes through altered mRNA stability.