title: 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.
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.|Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Maria
authors: M
authors: Filippova
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.|Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Whitney
authors: W
authors: Evans
authors: Department of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA 92354.
authors: Robert
authors: R
authors: Aragon
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Valery
authors: V
authors: Filippov
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.|Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Vonetta M
authors: VM
authors: Williams
authors: Department of Gynecology and Obstetrics, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Linda
authors: L
authors: Hong
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.|Department of Surgery, Loma Linda University School of Medicine, and Surgical Oncology Research Laboratory, Loma Linda VA Medical Center, Loma Linda, CA 92354.
authors: Mark E
authors: ME
authors: Reeves
authors: Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92354.|Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Loma Linda, CA 92354.
authors: Penelope
authors: P
authors: Duerksen-Hughes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D064593:Heterografts; D052162:Human papillomavirus 16 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012326:RNA Splicing; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000821:virology*
chemical_list: C068651:E6 protein, Human papillomavirus type 16; D009856:Oncogene Proteins, Viral; D020033:Protein Isoforms; D012097:Repressor Proteins
keywords: Cervical cancer; E6; E6(⁎); HPV 16; In vivo; Tumor