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

Abstract 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 C33A (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 C33A 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.