The small splice variant of HPV16 E6, E6*, reduces tumor formation in cervical carcinoma xenografts

High-risk types of human papillomavirus (HPV) cause nearly all cases of cervical cancer. The E6 oncoprotein is produced as a full-length variant (E6) as well as several shorter isoforms (E6*). E6* inhibits certain oncogenic activities of E6, suggesting that it might play an anti-oncogenic role in vivo. To test this, we created E6*-expressing SiHa (HPV+) and 03A (HPV-) cells, then examined the ability of both the parental and E6*-expressing cells to form tumors in nude mice. We found that over-expression of E6* indeed decreased the growth of tumors derived from both SiHa and 03A cells, with the reduction greatest in tumors derived from E6*-expressing SiHa cells. These findings point to multiple anti-oncogenic characteristics of E6*, some of which likely involve down-regulation of the full-length isoform, and others that are independent of HPV. These data represent the first demonstration of biologically-relevant E6* activities distinct from those of the full-length isoform in vivo. (C) 2013 Elsevier Inc. All rights reserved.