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...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2014-02, Vol.450, p.153-164
Main Authors: Filippova, Maria, Evans, Whitney, Aragon, Robert, Filippov, Valery, Williams, Vonetta M, Hong, Linda, Reeves, Mark E, Duerksen-Hughes, Penelope
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Cell Line, Tumor
Cervical cancer
Down-Regulation
E6
Female
Heterografts
HPV 16
Human papillomavirus 16 - genetics
Human papillomavirus 16 - metabolism
Humans
In vivo
Infectious Disease
Mice
Mice, Nude
Molecular Sequence Data
Oncogene Proteins, Viral - genetics
Oncogene Proteins, Viral - metabolism
Protein Isoforms - genetics
Protein Isoforms - metabolism
Repressor Proteins - genetics
Repressor Proteins - metabolism
RNA Splicing
Sequence Alignment
Tumor
Uterine Cervical Neoplasms - pathology
Uterine Cervical Neoplasms - virology
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2013.12.011