The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR.
- Author:
Tae Yeon KIM
1
;
Chan Joo KIM
;
Eun Joo KIM
;
Tae Chul PARK
;
Sung Eun NAMKOONG
;
Jae Gahb PARK
;
Soo Jong UM
;
Jong Sup PARK
Author Information
1. Department of Obstetrics & Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea. jspark@cmc.cuk.ac.kr
- Publication Type:Original Article
- Keywords:
Human papillomavirus (HPV);
Mutation;
Retinoic acid;
IFN-gamma
- MeSH:
Binding Sites;
Cell Line*;
DNA;
Human papillomavirus 16;
Human papillomavirus 18;
Interferon-gamma;
Plasmids;
Point Mutation;
Transfection;
Tretinoin;
Uterine Cervical Neoplasms*
- From:Journal of the Korean Cancer Association
2000;32(5):884-894
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
PURPOSE: We investigated the effects of all-trans-retinoic acid (ATRA) and/or interferon-gamma (IFN-gamma) on the growth of various cervical cancer cell lines and HPV E6/E7 expression. The relationships between the functional activities of HPV-URR and the growth inhibition were identified. MATERIALS AND METHODS: Four groups of cell lines were included; i) with integrated form of HPV-16 DNA (SNU-17, CaSki), ii) episomal form of HPV-16 (SNU-523), iii) integrated form of HPV-18 (SNU-1160, HeLa) and iv) episomal form of HPV-18 (SNU-1245). The promoter activity of HPV-URR was confirmed by transient transfection assay in C33A using the HPV-18 URR-CAT reporter plasmid. RESULTS: Selective mutation was detected in TEF-1 (transcriptional enhancer factor) binding site in SNU-17, and the activity of URR in SNU-17 was higher than that of the prototype. The proliferation was more inhibited in SNU-17 by IFN-gamma (10 ng/ml) than in SNU-902, CaSki and HeLa. The increase of the HPV-URR activity might play a role in the inhibition of growth by interferon-g. The expression of HPV-16 E6/E7 were significantly decreased by ATRA or IFN-gamma. CONCLUSION: Point mutation at TEF-1 binding site of SNU-17 was related with the increased transcriptional activity of URR. Mutation in the HPV-URR and alteration of HPV-URR activity in SNU-17 might be related with significant growth suppression by IFN-gamma.