J Korean Cancer Assoc.  2000 Oct;32(5):884-894.

The Effects of Interferon/Retinoic Acid on Cervical Cancer Cell Lines According to the Mutational Status of HPV-URR

• Kim TY
• Kim CJ
• Kim EJ
• Park TC
• Namkoong S
• Park JG
• Um SJ
• Park JS

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.

Keyword

Human papillomavirus (HPV); Mutation; Retinoic acid; IFN-gamma

MeSH Terms

Binding Sites
Cell Line*
DNA
Human papillomavirus 16
Human papillomavirus 18
Interferon-gamma
Plasmids
Point Mutation
Transfection
Tretinoin
Uterine Cervical Neoplasms*
DNA
Interferon-gamma
Tretinoin