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J Korean Cancer Assoc > Volume 32(5); 2000 > Article
Journal of the Korean Cancer Association 2000;32(5): 884-894.
The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR
Tae Yeon Kim, Chan Joo Kim, Eun Joo Kim, Tae Chul Park, Sung Eun Namkoong, Jae Gahb Park, Soo Jong Um, Jong Sup Park
1Department of Obstetrics & Gynecology, College of Medicine, The Catholic University of Korea, Seoul, Korea. jspark@cmc.cuk.ac.kr
2Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea.
3Deptartment of Surgery, Seoul National University, Medical college, Seoul, Korea.
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.
Key words: Human papillomavirus (HPV);Mutation;Retinoic acid;IFN-gamma
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