Mitomycin C modulates DNA-double strand break repair genes in cervical carcinoma cells.
In a previous study, we elucidated the apoptotic mechanism mediated via Fas/FasL-dependent pathway in mitomycin C-treated cervical carcinoma cells. In this study, 2-D and MALDI-TOF analyses were performed in order to search mitomycin C-induced modulators in cervical carcinoma cells. Some protein spots down- or up-regulated by mitomycin C were separately selected from the 2-D gels. Twenty protein spots were identified from the 2-D gels. Among the 20 spots, 11 spots were down-regulated, whereas 9 spots were up-regulated in SiHa/pRSV-luc cells by mitomycin C. Three spots have not been identified in the database. Ku70-binding protein (KUB3), MHC class I antigen, MHC class I chain-related protein A or multi-PDZ domain protein 1, MAGUK P55 subfamily member 3 or lamda/iota protein kinase C-interacting protein, and GL014 or Sad1/unc-84 protein-like 1 were suppressed by mitomycin C treatment. Heat shock 60 kDa protein 1 (chaperonin), similar to heat shock protein 90 kDa protein alpha or nine in centrosomal protein isoform C, NADP-dependent malic enzyme, mitochondrial precursor, GRB10 adaptor protein, glycogenin-interacting protein 1, cystathionine gamma-lyase, G2/mitotic-specific cyclin B2 or heat shock 90 kDa protein 1 alpha, peptidyl-prolyl cis-trans isomerase B, and PARP-2 (fragment) were induced by mitomycin C. KUB3, Brca1, and E6 gene expressions were down-regulated by mitomycin C in HPV-positive cervical cancer cells, SiHa/pRSV-luc and SiHa. In these studies, we suggest that MMC down-regulated the expression levels of the upstream molecules of DNA-double strand break repair system, non-homologous end joining or homologous recombination, resulting in the suppression of cervical cancer cell growth.
Kang
Yun Hee
YH
Laboratory of Cell and Immuno-biochemistry, Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong 1, Gwangjin-gu, Seoul, 143-701, South Korea.
Lee
Kyung-Ae
KA
Kim
Jung-Hee
JH
Park
Sung-Goo
SG
Yoon
Do-Young
DY
D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000187:drug effects* / Q000235:genetics; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects*; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D005260:Female; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology
D016685:Mitomycin; D004247:DNA